1. Carcinogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into
cancer cells. It is characterized by a progression of changes on cellular and genetic level that ultimately
reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.
Cell division is a physiological process that occurs in almost all tissues and under many circumstances. Under
normal circumstances, the balance between proliferation and programmed cell death, usually in the form
of apoptosis, is maintained by tightly regulating both processes to ensure the integrity of organs and tissues.
Mutations in DNA that lead to cancer (only certain mutations can lead to cancer and the majority of potential
mutations will have no bearing) disrupt these orderly processes by disrupting the programming regulating the
processes.
Carcinogenesis is caused by this mutation of the genetic material of normal cells, which upsets the normal
balance between proliferation and cell death. This results in uncontrolled cell division
Proto-oncogenes are genes that promote cell growth and mitosis, whereas tumor suppressor genes discourage
cell growth, or temporarily halt cell division to carry out DNA repair. Typically, a series of several mutations to
these genes is required before a normal cell transforms into a cancer cell.
One of the first oncogenes to be defined in cancer research is the ras oncogene.
Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth.
Generally, tumor suppressors are transcription factors that are activated by cellular stress or DNA damage.
Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will
trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such
genes is to arrest the progression of the cell cycle in order to carry out DNA repair, preventing mutations from
being passed on to daughter cells. The p53 protein, one of the most important studied tumor suppressor genes,
is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage.
For instance, individuals who inherit one mutant p53 allele (and are therefore heterozygous for mutated p53)
can develop melanomas and pancreatic cancer, known asLi-Fraumeni syndrome. Other inherited tumor
suppressor gene syndromes include Rb mutations, linked to retinoblastoma, and APC gene mutations, linked
to adenopolyposis colon cancer. Adenopolyposis colon cancer is associated with thousands of polyps in colon
while young, leading to colon cancer at a relatively early age. Finally, inherited mutations
in BRCA1 and BRCA2 lead to early onset of breast cancer.
A disregulation of the cell cycle components may lead to tumor formation. As mentioned above, some genes
like the cell cycle inhibitors, RB, p53 etc., when they mutate, may cause the cell to multiply uncontrollably,
forming a tumor.
Epidemiology indices the data collection tools that aid in the measurement and evaluation of disease
indicators and conditions; classification systems featuring numbered scales against which a specific population
may be compared.
The main types of cancer leading to overall cancer mortality each year are:
• lung (1.3 million deaths/year)
• stomach (803 000 deaths)
• colorectal (639 000 deaths)
• liver (610 000 deaths)
• breast (519 000 deaths).

2. What causes cancer?
Cancer arises from one single cell. The transformation from a normal cell into a tumour cell is a
multistage process, typically a progression from a pre-cancerous lesion to malignant tumours. These
changes are the result of the interaction between a person's genetic factors and three categories of
external agents, including:
• physical carcinogens, such as ultraviolet and ionizing radiation
• chemical carcinogens, such as asbestos, components of tobacco smoke, aflatoxin (a food
contaminant) and arsenic (a drinking water contaminant)
• biological carcinogens, such as infections from certain viruses, bacteria or parasites.
Some examples of infections associated with certain cancers:
• Viruses: hepatitis B and liver cancer, Human Papilloma Virus (HPV) and cervical cancer, and human
immunodeficiency virus (HIV) and Kaposi sarcoma.
• Bacteria: Helicobacter pylori and stomach cancer.
• Parasites: schistosomiasis and bladder cancer.
Ageing is another fundamental factor for the development of cancer. The incidence of cancer rises
dramatically with age, most likely due to a buildup of risks for specific cancers that increase with age.
The overall risk accumulation is combined with the tendency for cellular repair mechanisms to be less
effective as a person grows older.
Tobacco use, alcohol use, low fruit and vegetable intake, and chronic infections from hepatitis B (HBV),
hepatitis C virus (HCV) and some types of Human Papilloma Virus (HPV) are leading risk factors for
cancer in low- and middle-income countries. Cervical cancer, which is caused by HPV, is a leading
cause of cancer death among women in low-income countries.

3. A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be
confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from
a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office.
Biopsies of other organs are performed under anesthesia and require surgery in an operating room.
The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade,
genetic abnormalities, and other features of the tumor. Together, this information is useful to evaluate
the prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are
other types of testing that the pathologist may perform on the tissue specimen. These tests may provide
information about the molecular changes (such as mutations, fusion genes, and
numerical chromosome changes) that has happened in the cancer cells, and may thus also indicate the future
behavior of the cancer (prognosis) and best treatment.
In pathology, grading is a measure of the progress of tumors and other neoplasms. Some pathology grading
systems apply only to malignant neoplasms (cancer); others apply also to benign neoplasms. Theneoplastic
grading is a measure of cell anaplasia (lack of differentiation) in the sampled tumors arising from
the hyperplasia of normal tissue.
Pathology grading systems classify the microscopic cell appearance abnormality, deviations in their rate of
growth, degree of invasiveness and dissemination with the goal of predicting developments at tissue level (see
also the 4 major histological changes in dysplasia).
Cancer is a disorder of cell life cycle alteration that leads (non-trivially) to excessive cell proliferation rates,
typically longer cell lifespans and poor differentiation. The grade score (numerical: G1 up to G4) increases with
the lack of cellular differentiation - it reflects how much the tumor cells differ from the cells of the normal tissue
they have originated from (see 'Categories' below). Tumors may be graded on four-tier, three-tier, or two-tier
scales, depending on the institution and the tumor type.
The histologic tumor grade score along with the metastatic (whole-body-level cancer-spread) staging are used
to evaluate each specific cancer patient, develop their individual treatment strategy and to predict their
prognosis. A cancer that is very poorly differentiated is called anaplastic.
The most commonly used system of grading is as per the guidelines of the American Joint Commission on
Cancer.[citation needed] As per their standards, the following are the grading categories.
• GX Grade cannot be assessed
• G1 Well differentiated (Low grade)
• G2 Moderately differentiated (Intermediate grade)
• G3 Poorly differentiated (High grade)
• G4 Undifferentiated (High grade)
Grading systems are also different for each type of cancer.
The Gleason system[1], named after Donald Floyd Gleason, used to grade the adenocarcinoma cells in
prostate cancer is the most famous. This system uses a grading score ranging from 2 to 10. Lower Gleason
scores describe well-differentiated less aggressive tumors.
Tumor-Host Interactions
Tumors are surrounded by resident non-cancerous cells, connective tissue, and extracellular matrix.
These components are known as the tumor stroma or microenvironment.

4. Tumor Microenvironment Introduction
• The tumor microenvironment consists of four components:
• Cancer cells
• Non-cancer cells
• Secreted soluble factors
• Non-cellular, solid material
• The actual composition of the tumor microenvironment is highly variable.
Conditions within the tumor microenvironment
• Low oxygen levels (hypoxia), acidic conditions (low pH), and low sugar (glucose) levels are common conditions
in tumors.
• Conditions within the tumor microenvironment affect both cancer cells and normal cells.
• The tissue within and surrounding a tumor is often disorganized.
Inflammatory Cells in Cancer
• The immune system can inhibit or promote tumor growth.
• Many cancers are associated with chronic inflammatory conditions that activate cells of the innate immune
system.
• Macrophages secrete factors that enhance tumor cell proliferation, invasion, and promote angiogenesis.
Fibroblasts in Cancer
• Fibroblasts are the predominant cells in the stroma.
• Changes in fibroblast behavior are associated with tumor progression.
• Matrix metalloproteinases (MMPs) produced by fibroblasts degrade the extracellular matrix.
• MMPs are key players in cancer initiation, metastasis, and angiogenesis.
The Tumor Stroma and Metastasis
• Seed and Soil hypothesis: given tumor cells (seeds) can only colonize particular distant tissues (soil) that have a
suitable growth environment.
• Two key events must occur for site-specific metastasis to occur: 1) formation of a viable landing spot and 2)
expression of appropriate genes in the tumor cells.
• Tumor cells may invade foreign tissue but fail to colonize it. The reasons for this are unknown. These cells are
considered 'dormant' cancer cells.
The T cell is the primary cell responsible for direct recognition and killing of tumor cells. T cells carry out
immunologic surveillance, then proliferate and destroy newly transformed tumor cells after recognizing TAAs.
The T-cell response to tumors is modulated by other cells of the immune system; some cells require the
presence of humoral antibodies directed against the tumor cells (antibody-dependent cellular cytotoxicity) to
initiate the interactions that lead to the death of tumor cells. In contrast, suppressor T cells inhibit the immune
response against tumors.
Cytotoxic T lymphocytes (CTLs) recognize antigens on target cells and lyse these cells. These antigens may
be cell surface proteins or may be intracellular proteins (eg, TAAs) that are expressed on the surface in
combination with class I major histocompatibility complex (MHC) molecules. Tumor-specific CTLs have been
found with neuroblastomas; malignant melanomas; sarcomas; and carcinomas of the colon, breast, cervix,
endometrium, ovary, testis, nasopharynx, and kidney.
Natural killer (NK) cells are another population of effector cells with tumoricidal activity. In contrast to CTLs,
NK cells lack the receptor for antigen detection but can still recognize normal cells infected with viruses or
tumor cells. Their tumoricidal activity is termed “natural” because it is not induced by a specific antigen. The
mechanism by which NK cells discriminate between normal and abnormal cells is under study. Evidence
suggests that class I MHC molecules on the surface of normal cells inhibit NK cells and prevent lysis. Thus, the
decreased level of class I molecule expression characteristic of many tumor cells may allow activation of NK
cells and subsequent tumor lysis.
Macrophages can kill specific tumor cells when activated by a combination of factors, including lymphokines
(soluble factors produced by T cells) and interferon. They are less effective than T-cell–mediated cytotoxic
mechanisms. Under certain circumstances, macrophages may present TAAs to T cells and stimulate tumor-
specific immune response.
Dendritic cells are dedicated antigen-presenting cells present in barrier tissues (eg, skin, lymph nodes). They
play a central role in initiation of tumor-specific immune response. These cells take up tumor-associated

5. proteins, process them, and present TAAs to T cells to stimulate the CTL response against tumor. The presence
of dendritic cells in tumor tissues correlates with improved prognosis.
Lymphokines produced by immune cells stimulate growth or induce activities of other immune cells. Such
lymphokines include IL-2, also known as T-cell growth factor, and the interferons. IL-12 is produced by dendritic
cells and specifically induces CTLs, thereby enhancing antitumor immune responses.
Regulatory T cells are normally present in the body and help prevent autoimmune reactions. They are
produced during the active phase of immune responses to pathogens and limit the strong immune response
that could damage the host. Accumulation of these cells in cancers inhibits antitumor immune responses.
Myeloid-derived suppressor cells consist of immature myeloid cells and their precursors. These cells
accumulate in large numbers in cancers and potently suppress immune responses.
Humoral Immunity
In contrast to T-cell cytotoxic immunity, humoral antibodies do not appear to confer significant protection against
tumor growth. Most antibodies cannot recognize TAAs.
metastatic disease
Some cancer cells also acquire the ability to penetrate and infiltrate surrounding normal tissues in the local
area, forming a new tumor. The newly formed "daughter" tumor in the adjacent site within the tissue is called a
local metastasis.
Some cancer cells acquire the ability to penetrate the walls of lymphatic and/or blood vessels, after which they
are able to circulate through the bloodstream (circulating tumor cells) to other sites and tissues in the body. This
process is known (respectively) as lymphatic or hematogeneous spread.
Metastasis occurs by four routes:

6. 1. Spread into body cavities. This occurs by the seeding surface of the peritoneul, plural, pericardial or
subarchnoid spaces. For example, carcinoma of the ovary spreads transperitoneally to the surface of
the liver.
2. Invasion of lymphatics. This is followed by the transport of tumor cells to regional nodes and ultimately
to other parts of the body; it is common in initial spread of carcinomas.
3. Hematogenous spread. This is typical of all sarcomas but it is the favored route in certain carcinomas
(e.g. those originating in kidneys). Because of their thinner walls veins are more frequently invaded
than arteries and metastasis follows the pattern of the venous flows.
4. Transplantation. Mechanical carriage of fragments of tumor cells by surgical instruments during
operation or the use of needles during diagnostic procedures.

7. Tumor antigen is an antigenic substance produced in tumor cells, i.e., it triggers an immune response in
the host. Tumor antigens are useful in identifying tumor cells and are potential candidates for use in cancer
therapy.
Normal proteins in the body are not antigenic because of self-tolerance, a process in which self-reacting
cytotoxic T lymphocytes (CTLs) and autoantibody-producing B lymphocytes are culled "centrally" in primary
lymphatic tissue (BM) and "peripherally" in secondary lymphatic tissue (mostly thymus for T-cells
and spleen/lymph nodes for B cells). Thus any protein that is not exposed to the immune system triggers an
immune response.
Any protein produced in a tumor cell that has an abnormal structure due to mutation can act as a tumor antigen.
Such abnormal proteins are produced due to mutation of the concerned gene. Mutation
ofprotooncogenes and tumor suppressors which lead to abnormal protein production are the cause of the tumor
and thus such abnormal proteins are called tumor-specific antigens. Examples of tumor-specific antigens
include the abnormal products of ras and p53 genes. In contrast, mutation of other genes unrelated to the
tumor formation may lead to synthesis of abnormal proteins which are called tumor-associated antigens.
Proteins that are normally produced in very low quantities but whose production is dramatically increased in
tumor cells, trigger an immune response. An example of such a protein is the enzyme tyrosinase, which is
required for melanin production. Normally tyrosinase is produced in minute quantities but its levels are very
much elevated in melanoma cells.
Oncofetal antigens are another important class of tumor antigens. Examples are alphafetoprotein (AFP)
and carcinoembryonic antigen (CEA). These proteins are normally produced in the early stages of embryonic
development and disappear by the time the immune system is fully developed. Thus self-tolerance does not
develop against these antigens.
Abnormal proteins are also produced by cells infected with oncoviruses, eg. EBV and HPV. Cells infected by
these viruses contain latent viral DNA which is transcribed and the resulting protein produces an immune
response.
Immunodiagnosis:
Tumor Associated Antigens (TAAs) can help diagnose various tumors and sometimes determine the response
to therapy or recurrence. An ideal tumor marker would be released only from tumor tissue, be specific for a
given tumor type, be detectable at low levels of tumor cell burden, have a direct relationship to the tumor cell
burden, and be present in all patients with the tumor. However, although most tumors release detectable
antigenic macromolecules into the circulation, no tumor marker has all the requisite characteristics to provide
enough specificity or sensitivity to be used in early diagnosis or mass cancer screening programs.
Carcinoembryonic antigen (CEA) is a protein-polysaccharide complex present in colon carcinomas and in
normal fetal intestine, pancreas, and liver. Blood levels are elevated in patients with colon carcinoma, but the
specificity is relatively low because positive results also occur in heavy cigarette smokers and in patients with
cirrhosis, ulcerative colitis, and other cancers (eg, breast, pancreas, bladder, ovary, cervix). Monitoring CEA
levels may be useful for detecting cancer recurrence after tumor excision if the patient initially had an elevated
CEA and for refining estimates of prognosis by stage.
α-Fetoprotein, a normal product of fetal liver cells, is also present in the sera of patients with primary
hepatoma, nonseminomatous germ cell tumors, and, frequently, ovarian or testicular embryonal carcinoma.
Levels are sometimes useful for estimating prognosis or, less often, for diagnosis.
β Subunit of human chorionic gonadotropin (β-hCG), measured by immunoassay, is the major clinical
marker in women with gestational trophoblastic neoplasia (GTN)—a disease spectrum that includes
hydatidiform mole, nonmetastatic GTN, and metastatic GTN (see also Gynecologic Tumors: Gestational
Trophoblastic Disease)—and in about two thirds of men with testicular embryonal carcinoma or
choriocarcinoma. The β subunit is measured because it is specific for hCG. This marker is present in low levels
in healthy people. Levels are elevated during pregnancy.

8. Prostate-specific antigen (PSA), a glycoprotein located in ductal epithelial cells of the prostate gland, can be
detected in low concentrations in the sera of healthy men. Using an appropriate upper limit of normal, assays
with monoclonal antibodies detect elevated serum levels of PSA in about 90% of patients with advanced
prostate cancer, even in the absence of defined metastatic disease. It is more sensitive than prostatic acid
phosphatase. However, because PSA is elevated in other conditions (eg, benign prostatic hypertrophy,
prostatitis, recent GU tract instrumentation), it is less specific. PSA can be used to monitor recurrence after
prostatic carcinoma has been diagnosed and treated.
CA 125 is clinically useful for screening, diagnosing, and monitoring therapy for ovarian cancer, although any
peritoneal inflammatory process and some other cancers can increase levels.
β2-Microglobulin is often elevated in multiple myeloma and in some lymphomas. Its primary use is in
prognosis.
CA 19-9 was originally developed to detect colorectal cancer but proved more sensitive for pancreatic cancer. It
is primarily used to judge the response to treatment in patients with advanced pancreatic cancers. CA 19-9 can
also be elevated in other GI cancers, particularly cancer of the bile ducts, and some benign bile duct and
cholestatic disorders.
CA 15-3 and CA 27-29 are elevated in most patients with metastatic breast cancer. Levels may also be
elevated in other conditions. These markers are primarily used to monitor the response to therapy.
Chromogranin A is used as a marker for carcinoid and other neuroendocrine tumors. Sensitivity and specificity
for neuroendocrine tumors can exceed 75%, and diagnostic accuracy is higher with diffuse than with localized
tumors. Levels can be elevated in other cancers, such as lung and prostate, and some benign disorders (eg,
primary hypertension, chronic kidney disease, chronic atrophic gastritis).
Thyroglobulin is produced by the thyroid and may be elevated with various thyroid disorders. It is primarily
used after complete thyroidectomy to detect recurrent thyroid cancer and to follow the response to treatment in
metastatic thyroid cancer.
TA-90 is a highly immunogenic subunit of a urinary tumor–associated antigen that is present in 70% of
melanomas, soft-tissue sarcomas, and carcinomas of the breast, colon, and lung. Some studies have shown
that TA-90 levels can accurately predict survival and the presence of subclinical disease after surgery for
melanoma.
Cancer immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the
patient's immune system to attack the malignant tumor cells that are responsible for the disease. This can be
either through immunization of the patient (eg. by administering a cancer vaccine, such as
Dendreon's Provenge), in which case the patient's own immune system is trained to recognize tumor cells as
targets to be destroyed, or through the administration of therapeutic antibodies as drugs, in which case the
patient's immune system is recruited to destroy tumor cells by the therapeutic antibodies.
Antibodies are a key component of the adaptive immune response, playing a central role in both in the
recognition of foreign antigens and the stimulation of an immune response to them. It is not surprising therefore,
that many immunotherapeutic approaches involve the use of antibodies. The advent of monoclonal
antibody technology has made it possible to raise antibodies against specific antigens such as the unusual
antigens that are presented on the surfaces of tumors.
Cancer immunotherapy:Monoclonal antibodies
Brand Approval
Antibody Type Target Approved treatment(s)
name date
Alemtuzumab Campath 2001 humanized CD52 Chronic lymphocytic leukemia
vascular
Bevacizumab Avastin 2004 humanized endothelial colorectal cancer
growth factor
epidermal
Cetuximab Erbitux 2004 chimeric growth factor colorectal cancer
receptor

9. Gemtuzumab acute myelogenous
Mylotarg 2000 humanized CD33
ozogamicin leukemia (with calicheamicin)
non-Hodgkin
Ibritumomab
Zevalin 2002 murine CD20 lymphoma (with yttrium-90 or i
tiuxetan
ndium-111)
epidermal
Panitumumab Vectibix 2006 human growth factor colorectal cancer
receptor
Rituxan,
Rituximab 1997 chimeric CD20 non-Hodgkin lymphoma
Mabthera
Trastuzumab Herceptin 1998 humanized ErbB2 breast cancer

10. The TNM Classification of Malignant Tumours (TNM) is a cancer staging system that describes the extent
of cancer in a patient’s body.
• T describes the size of the tumour and whether it has invaded nearby tissue,
• N describes regional lymph nodes that are involved,
• M describes distant metastasis (spread of cancer from one body part to another).
he general outline for the TNM classification is below. The values in parentheses give a range of what can be
used for all cancer types, but not all cancers use this full range.
[edit]Mandatory parameters ("T", "N", and "M")
• T (a, CIS,(0),1–4): size or direct extent of the primary tumor
• N (0–3): degree of spread to regional lymph nodes
• N0: tumor cells absent from regional lymph nodes
• N1: regional lymph node metastasis present; (at some sites: tumor spread to closest or small
number of regional lymph nodes)
• N2: tumor spread to an extent between N1 and N3 (N2 is not used at all sites)
• N3: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all
sites)
• M (0/1): presence of metastasis
• M0: no distant metastasis
• M1: metastasis to distant organs (beyond regional lymph nodes)
Use of an "X" instead of a number or other suffix means that the parameter was not assessed.
Some of the aims for adopting a global standard are to:
• Aid medical staff in staging the tumour helping to plan the treatment.
• Give an indication of prognosis.
• Assist in the evaluation of the results of treatment.
• Enable facilities around the world to collate information more productively.
TNM Breast cancer
The T stages (tumour)
TX means that the tumour size cannot be assessed
T1 - The tumour is no more than 2 centimetres (cm) across
T1 is further divided into 4 groups
• T1mic - under a microscope the cancer cells can be seen to spread less than 0.1cm into
surrounding tissue (microinvasion)
• T1a - the tumour is more than 0.1 cm but not more than 0.5 cm
• T1b - the tumour is more than 0.5 cm but not more than 1 cm
• T1c - the tumour is more than 1 cm but not more than 2 cm
T2 - The tumour is more than 2 centimetres, but no more than 5 centimetres across
T3 - The tumour is bigger than 5 centimetres across
T4 is divided into 4 groups
• T4a - The tumour has spread into the chest wall

11. • T4b - The tumour has spread into the skin
• T4c - The tumour is fixed to both the skin and the chest wall
• T4d - Inflammatory carcinoma - this is a cancer in which the overlying skin is red, swollen and
painful to the touch
The N stages (nodes)
NX means that the lymph nodes cannot be assessed (for example, if they were previously removed)
N0 - No cancer cells found in any nearby nodes
N1 - Cancer cells are in nodes in the armpit but the nodes are not stuck to surrounding tissues
N2 is divided into 2 groups
• N2a - there are cancer cells in the lymph nodes in the armpit, which are stuck to each other and
to other structures
• N2b - there are cancer cells in the lymph nodes behind the breast bone (the internal mammary
nodes). These have either been seen on a scan or felt by the doctor. There is no evidence of
cancer in lymph nodes in the armpit
N3 is divided into 3 groups
• N3a - there are cancer cells in lymph nodes below the collarbone
• N3b - there are cancer cells in lymph nodes in the armpit and under the breast bone
• N3c - there are cancer cells in lymph nodes above the collarbone
The M stages (metastases)
M0 - No sign of cancer spread
M1 - Cancer has spread to another part of the body, apart from the breast and lymph nodes under the
arm

12. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.
Combined modality chemotherapy is the use of drugs with other cancer treatments, such as radiation
therapy or surgery. Most cancers are now treated in this way. Combination chemotherapy is a similar practice
that involves treating a patient with a number of different drugs simultaneously. The drugs differ in their
mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any
one agent.
In neoadjuvant chemotherapy (preoperative treatment) initial chemotherapy is designed to shrink the primary
tumour, thereby rendering local therapy (surgery or radiotherapy) less destructive or more effective.
Adjuvant chemotherapy (postoperative treatment) can be used when there is little evidence of cancer present,
but there is risk of recurrence. This can help reduce chances of developing resistance if the tumour does
develop. It is also useful in killing any cancerous cells which have spread to other parts of the body. This is
often effective as the newly growing tumours are fast-dividing, and therefore very susceptible.
Palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life
expectancy. For these regimens, a better toxicity profile is generally expected.
All chemotherapy regimens require that the patient be capable of undergoing the treatment.
Chemotherapy drugs are classified based on how they work. The main types of chemotherapy drugs are
described below:
• Alkylating drugs kill cancer cells by directly attacking DNA, the genetic material of the genes.
Cyclophosphamide is an alkylating drug.
• Antimetabolites interfere with the production of DNA and keep cells from growing and multiplying. An
example of an antimetabolite is 5-fluorouracil (5-FU).
• Antitumor antibiotics are made from natural substances such as fungi in the soil. They interfere with
important cell functions, including production of DNA and cell proteins. Doxorubicin and bleomycin
belong to this group of chemotherapy drugs.
• Plant alkaloids prevent cells from dividing normally. Vinblastine and vincristine are plant alkaloids
obtained from the periwinkle plant.
• Steroid hormones slow the growth of some cancers that depend on hormones. For example,
tamoxifen is used to treat breast cancers that depend on the hormone estrogen for growth.

13. Alkylating agents cause cell death by interacting with DNA during cell synthesis. DNA is the component of cells
containing all the genetic information the cell needs to grow, divide and function. The DNA is like the blue-print of living
cells and has a special helical ladder structure. Alkylating agents work by directly interacting with exposed DNA and
adding alkyl groups. The resulting permanent DNA damage ultimately results in death of the cells.
Cyclophosphamide (cycloblastin, endoxan) was the first clinically effective cancer chemotherapy agent and is the most
commonly used alkylating agent. As well as its anti-tumour effects, it also has immunosuppressant activity as it also
disrupts the function of lymphocytes (immune cells).
Other alkylating agents include chlorambucil (leukeran), carmustine, lomustine and cisplatin. The latter is sometimes
classed as a platinum compound and has been responsible for the massive advances in the treatment of testicular
cancer as well as being effective against a range of other cancers including lung, ovarian and head and neck cancers.
Side effects of alkylating agents
All alkylating agents depress bone marrow function and cause gastrointestinal disturbances such as nausea and
vomiting. As bone marrow is responsible for the production of red blood cells, white blood cells and platelets when it is
depressed symptoms of anaemia, infection and bleeding respectively, may occur. Therefore regular monitoring ofblood
counts is required during treatment. The frequency and severity of most adverse effects increase with increasing dose.
Sterility and secondary malignancies have been reported with prolonged use of alkylating agents.
Anti-metabolites are molecules that have very similar structures to true proteins within cells. They are therefore taken up
by cells which cannot distinguish the drug from the real protein. Once inside the cell, anti-metabolites interact with DNA

14. and RNA like the normal protein would but due to slight variations in their properties prevent the cell processes from
continuing. Anti-metabolites therefore prevent normal proteins from binding in the cell and halt normal function and
division. In other words, they mimic and interfere with the binding of real proteins. Once again this leads to programmed
cell death (apoptosis).
The molecules mimicked by anti-metabolites include folate, purine and pyrimidine. These agents seem to be particularly
important in DNA synthesis and cellularmetabolism in cancer cells.
Folate antagonists
These agents mimic folate and enter the cell. They inhibit an enzyme called dihydrofolate reductase which is needed in
the production of amino acids and purine nucleotides, the building blocks of DNA, RNA and key cellular proteins.
Methotrexate is the main folate antagonist. It may be used in a variety of solid tumours and haematological malignancies.
In addition its immunosuppressant properties may be utilised in the treatment of non-malignant conditions such
as rheumatoid arthritis and psoriasis.
Side effects of folate antagonists
Methotrexate is very toxic at high doses, particularly to bone marrow and the digestive tract lining. Symptoms of toxicity
include:
•Bone marrow suppression, including bleeding, anaemia and increased risk of infection;
•Nausea;
•Anorexia;
•Diarrhoea raging from mild to severe ulceration and bleeding.
Methotrexate is often administered with leucovorin, which is an agent designed to reduce the anaemia and toxicity to
normal cells that often accompanies methotrexate therapy.
Purine antagonists
Purine antagonists mimic the purines adenine and guanine, two of the bases that make up DNA. By mimicking these
molecules, purine antagonists block DNA synthesis and prevent cell division. Examples of purine antagonists include 6-
mercaptopurine (Puri-Nethol), 6-thioguanine, dacarbazine and fludurabine. Purine antagonists are used for the treatment
of acute leukaemias.
Side effects of purine antagonists
The side effects of 6-mercaptopurine are listed below which are similar to those seen with many other chemotherapeutic
agents. They are rare in children.
•Bone marrow suppression, resulting in increased bleeding and infection risk;
•Mouth sores;
•Skin rash/acne;
•Mild nausea;
•Abnormal liver function;
•Hair loss.
Anorexia, fever, fatigue/weakness and facial flushing can also occur with other purine antagonists than 6-
mercaptopurine.
Pyrimidine antagonists
Pyrimidine antagonists mimic the pyrimidines cytosine and thymine, the other two bases making up nucleotides and
DNA. By mimicking these molecules, pyrimidine antagonists block DNA synthesis and prevent cell division in a similar
mechanism to purine antagonists.
The pyrimidine antagonists include 5-fluorouracil (Efudix), cytarabine, capecitabine (Xeloda) and gemcitabine (Gemzar).
5-Flurouracil has a major role in the treatment of gastrointestinal cancers. Capecitabine is an oral version of 5-

15. fluorouracil and is used in the treatment of metastatic colon cancer and metastatic or resistant breast cancer. Cytarabine
is used to treat leukaemias, and gemcitabine is used in solid cancers such as ovarian or in combination with cisplatin to
treat non-small cell lung cancer.
Side effects of pyrimidine antagonists
As 5-fluorouracil is active against dividing cells, it also kills healthy cells, which contributes to the following side effects:
•Tiredness
•Nausea and diarrhoea
•Bone marrow depression that may lead to anaemia
•Increased tendency to bruise
•Mouth sores
•Altered pigmentation of the skin
The side effects of capecitabine are similar, as it is converted to 5-fluorouracil once inside the body. Cytarabine may also
cause anorexia, fever and rash.

16. Anthracyclines are cytotoxic (cell killing) antibiotics that are also non-cell-cycle specific chemotherapy
agents. They are probably amoung the most commonly used cytotoxic drugs. Many antracyclines also have
immunosuppressant activity.
Doxorubicin (adriamycin) is an example of an anthracycline medication which is used in a variety of cancers
including affecting the breast, endometrium (lining of the
womb), ovary, testicle, thyroid, stomach, bladder, liver and lung, soft tissues and several childhood cancers.
Epirubicin and mitozantrone are other examples of anthracycline medications.
Side effects of anthracyclines
Side effects of anthracycline use include:
•Myelosuppression (bone marrow suppression) especially of white blood cells, but also of red blood cells and
platelets. These side effects of chemotherapy can be minimised with red blood cell and platelet transfusions.
In addition if you develop fever during treatment (febrile neutropenia) you must see a doctor for careful
management;
•Increased risk of infection and bleeding;
•Toxicity to the heart which may lead to arrhythmias. Damage may become permanent after approximately
one month of treatment especially if you have been previously exposed to these drugs. It is for this reason
that doctors are often reluctant to prescribe anthracyclines if you have been treated with them in the past;
•Severe local reactions, including tissue necrosis (death) or extravasation (leakage of drug outside the blood
vessels);
•Secondary malignancies;
•Radiation recall: The recurrence of skin damage from previous radiotherapy;
•Alopecia (hair loss): This may be associated with significant effects on quality of life;
•Nausea and vomiting;
•Oral ulceration.
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers
to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical
forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA. The drug is used in the
treatment ofHodgkin's lymphoma (as a component of the ABVD regimen), squamous cell carcinomas,
and testicular cancer, as well as in the treatment of plantar warts [1] and as a means of effecting pleurodesis
The most serious complication of bleomycin is pulmonary fibrosis and impaired lung function. It has been
suggested that bleomycin induces sensitivity to oxygen toxicity
The mitomycins are a family of aziridine-containing natural products isolated from Streptomyces
caespitosus or Streptomyces lavendulae.[1] One of these compounds,mitomycin C, finds use as
a chemotherapeutic agent by virtue of its antitumour antibiotic activity. It is given intravenously to treat upper
gastro-intestinal (e.g.esophageal carcinoma), anal cancers, and breast cancers, as well as by bladder
instillation for superficial bladder tumours. It causes delayed bone marrow toxicity and therefore it is usually
administered at 6-weekly intervals. Prolonged use may result in permanent bone-marrow damage. It may
also cause lung fibrosis and renal damage.
Actinomycin D is primarily used as an investigative tool in cell biology to inhibit transcription. It does this by
binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase.
[2] Because it can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals
such ashydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.
Actinomycin D, marketed under the trade name Dactinomycin, is one of the older chemotherapy drugs, and
has been used in therapy for many years.

17. It is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of
cancers including gestational trophoblastic neoplasia,Wilms' tumor and rhabdomyosarcoma.

18. Vinca alkaloids act on a specific phase of the cell cycle called metaphase (M phase). They are another class of anti-
tubulin agents (along with the taxanes) and work by binding tubulin and inhibiting the production of microtubules. This
halts cell division and leads to cell death. Vinca alkaloids are used to treat both haematological (diseases of blood cells
such as leukaemias) and non-haematological (solid organ) malignancies.
There are four vinca alkaloids currently available namely vinblastine, vincristine, vindesine and vinorelbine (Navelbine).
Side effects of vinca alkaloids
Vinca alkaloids cause a number of the common side effects seen with chemotherapy such as:
•Nausea and vomiting;
•Hair loss;
•Mouth sores;
•Headache;
•Constipation.
Vinblastine also causes bone marrow suppression like many other agents, resulting in increased bleeding, infection
and anaemia risk. In addition, vinca alkaloids can damage nerves. For example, vincristine may cause numbness,
sensory impairment, blurred or double vision and/or general weakness.
Podophyllotoxin is a plant-derived compound which is said to help with digestion as well as used to produce
two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the G1 phase(the start
of DNA replication) and the replication of DNA (the S phase). The exact mechanism of its action is not yet
known.
Taxanes
Taxanes are cytotoxic agents that work on a protein called tubulin found in the cytoplasm of cells. Tubulin is needed for
the production of microtubules which are essential in cell division. Microtubules help separate chromosomes (agents
carrying our DNA) when cells divide. Taxanes are generally used when other chemotherapy regimens have failed. They
tend to be effective against ovarian, breast and lung cancers.
Taxanes currently available in Australia include:
•Paclitaxel (Anzatax, Taxol);
•Nanoparticle albumin-bound paclitaxel (Abraxane); and
•Docetaxal (Taxotere).
Paclitaxel has been shown to have activity in a broad range of solid tumours.
Docetaxal is very similar to paclitaxel in terms of mechanism of action, metabolism, and elimination. It is currently
approved as second line therapy for advanced breast cancer and non-small cell lung cancer (NSCLC).
Nanoparticle albumin-bound paclitaxel is used for metastatic breast cancers. It binds the active component (paclitaxel) to
a protein (Albumin) normally found in the blood. This increases the drug's solubility and avoids the use of other additives,
associated with side effects, that normally act to increase the water solubility of the drug.
Side effects of taxanes
Taxanes cause bone marrow suppression like many other chemotherapeutic agents. The most common effect is
neutropaenia, which increases the chance of infection. Other side effects include:
•Nausea and vomiting
•Diarrhoea;
•Mouth sores;
•Joint and muscle aches;

19. •Cisplatin is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas,
some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors. It was
the first member of a class of anti-cancer drugs which now also includes carboplatin and oxaliplatin. These
platinum complexes react in vivo, binding to and causing crosslinking of DNA which ultimately
triggers apoptosis (programmed cell death).
Cisplatin is administered intravenously as short-term infusion in physiological saline for treatment of solid
malignacies.
cisplatin has a number of side-effects that can limit its use:
• Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient's creatinine
clearance (a measure of renal function) is reduced. Adequate hydration and diuresis is used to prevent
renal damage. The nephrotoxicity of platinum-class drugs seems to be related to reactive oxygen
species and in animal models can be ameliorated by free radical scavenging agents (e.g., amifostine).
Nephrotoxicity is a dose-limiting.
• Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and
after treatment.
• Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents, but this symptom
is managed with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination
withcorticosteroids. Aprepitant combined with ondansetron and dexamethasone has been shown to be
better for highly emetogenic chemotherapy than just ondansetron and dexamethasone.
• Ototoxicity (hearing loss): unfortunately there is at present no effective treatment to prevent this side
effect, which may be severe. Audiometric analysis may be necessary to assess the severity of
ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and
the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. The
ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to melanin in
the stria vascularis of the inner ear or the generation of reactive oxygen species.
• Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia.
The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is
not primarily due to the Cisplatin.
Procarbazine is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain
brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating
agents.
Asparaginase The rationale behind asparaginase is that it takes advantage of the fact that ALL leukemic cells
are unable to synthesize the non-essential amino acid asparagine, whereas normal cells are able to make their
own asparagine; thus leukemic cells require high amount of asparagine. These leukemic cells depend on
circulating asparagine. Asparaginase, however, catalyzes the conversion of L-asparagine to aspartic acid and
ammonia. This deprives the leukemic cell of circulating asparagine. The main side effect is an allergic or
hypersensitivity reaction; anaphylaxis is a possibility.[2] Asparaginase has also been associated
with pancreatitis.
Retinoids
Retinoids are drugs that are relatives of vitamin A. Retinoids control normal cell growth, cell
differentiation (the normal process of making cells different from each other), and cell death during
embryonic development and in certain tissues later in life. Retinoids effects on the cells are controlled
by receptors on the nucleus of each cell (nuclear receptors).
There are two major classes of retinoid nuclear receptors: retinoic acid receptors (RAR) and retinoid-X-
receptors (RXR). There are also subtypes within each class. Each of these types of receptors has different

20. functions in different tissues. The different retinoid drugs work by binding to different receptors; which, in turn,
affect cell growth and differentiation.
Retinoids are relatively new types of anti-cancer drugs. They have been used alone or in combination to treat a
variety of cancers such as skin cancers, cutaneous T-cell lymphoma, acute promyelocytic leukemia, lung
cancer, breast cancer, ovarian cancer, bladder cancer, kidney cancer, and head and neck cancers. Retinoids
have also been used experimentally in an attempt to prevent certain types of cancer. There is ongoing
research to determine their role in both cancer treatment and prevention.
Retinoids have been associated with side effects such as skin problems (dryness, peeling, itching, sun
sensitivity), reversible elevation in liver enzymes, temporary abnormal lipid levels, low thyroid levels
(hypothyroidism), and headaches.

21. Hormonal therapy is one of the major modalities of medical treatment for cancer, others being cytotoxic
chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine
systemthrough exogenous administration of specific hormones, particularly steroid hormones, or drugs which
inhibit the production or activity of such hormones (hormone antagonists). Because steroid hormones are
powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones
can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs,
such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.
Hormonal therapy is used for several types of cancers derived from hormonally responsive tissues, including
the breast, prostate, endometrium, and adrenal cortex.
One effective strategy for starving tumor cells of growth- and survival-promoting hormones is to use
drugs which inhibit the production of those hormones in their organ of origin.
Aromatase inhibitors
Aromatase inhibitors are an important class of drugs used for the treatment of breast
cancer in postmenopausal women. At menopause, estrogen production in the ovaries ceases, but other tissues
continue to produce estrogen through the action of the enzyme aromatase on androgens produced by
the adrenal glands. When the action of aromatase is blocked, estrogen levels in post-menopausal women can
drop to extremely low levels, causing growth arrest and/or apoptosis of hormone-responsive cancer
cells. Letrozole and anastrozoleare aromatase inhibitors which have been shown to be superior to tamoxifen for
the first-line treatment of breast cancer in postmenopausal women.[1] Exemestane is an irreversible
"aromatase inactivator" which is superior to megestrol for treatment of tamoxifen-refractory metastatic breast
cancer, and does not appear to have the osteoporosis-promoting side effects of other drugs in this class.[1]
Aminoglutethimide inhibits both aromatase and other enzymes critical for steroid hormone synthesis in
the adrenal glands. It was formerly used for breast cancer treatment, but has since been replaced by more
selective aromatase inhibitors. It can also be used for the treatment of hyperadrenocortical syndromes, such
as Cushing's syndrome and hyperaldosteronism in adrenocortical carcinoma.[1]
GnRH analogs
Analogs of gonadotropin-releasing hormone (GnRH) can be used to induce a chemical castration, that is,
complete suppression of the production of estrogen and progesterone from the female ovaries, or complete
suppression of testosterone production from the male testes. This is due to a negative feedback effect of
continuous stimulation of the pituitary gland by these hormones. Leuprolide and goserelin are GnRH analogs
which are used primarily for the treatment of hormone-responsive prostate cancer. Because the
initial endocrine response to GnRH analogs is actually hypersecretion of gonadal steroids, hormone receptor
antagonists such as flutamide are typically used to prevent a transient boost in tumor growth.[1]
Hormone receptor antagonists bind to the normal receptor for a given hormone and prevent its activation. The
target recepetor may be on the cell surface, as in the case of peptide and glycoprotein hormones, or it may be
intracellular, as in the case of steroid hormone receptors.
Selective estrogen receptor modulators
Selective estrogen receptor modulators (SERM's) are an important class of hormonal therapy agents which act
as antagonists of the estrogen receptor and are used primarily for the treatment and chemoprevention of breast
cancer. Some members of this family, such as tamoxifen, are actually partial agonists, which can
actuallyincrease estrogen receptor signalling in some tissues, such as the endometrium. Tamoxifen is currently
first-line treatment for nearly all pre-menopausal women with hormone receptor-positive breast cancer.

22. Antiandrogens
Antiandrogens are a class of drug which bind and inhibit the androgen receptor, blocking the growth- and
survival-promoting effects of testosterone on certain prostate cancers.Flutamide and bicalutamide are
antiandrogens which are frequently used in the treatment of prostate cancer, either as long-term monotherapy,
or in the initial few weeks of GnRH analog therapy

23. Interferons (IFNs) are proteins made and released by lymphocytes in response to the presence of pathogens
—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the
protective defenses of the immune system that eradicate pathogens or tumors.
IFNs have other functions: they activate immune cells, such as natural killer cells and macrophages; they
increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes; and they
increase the ability of uninfected host cells to resist new infection by virus. Certain host symptoms, such as
aching muscles and fever, are related to the production of IFNs during infection.
Imidazoquinoline is the main ingredient of Aldara (Imiquimod) cream, treatment for actinic keratosis,
superficial basal cell carcinoma, papilloma and external genital warts.
Interferon therapy is used (in combination with chemotherapy and radiation) as a treatment for many cancers.
[17] This treatment is most effective for treating hematological malignancy; leukemia and lymphomas
including hairy cell leukemia, chronic myeloid leukemia, nodular lymphoma, cutaneous T-cell lymphoma.
[17] Patients with recurrent melanomas receive recombinant IFN-α2b
Hematopoietic Growth Factors are a group of substances with the ability to support hematopoietic (blood cell) colony
formation in vitro. This group of substances includes erythropoietin, interleukin-3 and colony-stimulating factors (CSFs).
Erythropoietin stimulates production of erythrocytes, or red blood cells. Interleukin-3 and CSFs can mature cells, have
overlapping capabilities to affect progenitor cells (“parent” cells that will develop into a specific type of cell) of several
blood cell lines, and can also affect cells outside the hematopoietic system.
HGFs are used to promote bone marrow proliferation in aplastic anemia, following cytotoxic chemotherapy, or following a
bone marrow transplant.

25. It is possible to take hematopoietic stem cells from one person and then infuse them into another
person (Allogenic) or into the same person at a later time (Autologous). If donor and recipient are
compatible, these infused cells will then travel to the bone marrow and initiate blood cell production.
Transplantation from one person to another is performed in severe cases of disease of the bone marrow. The
patient's marrow is first killed off with drugs or radiation, and then the new stem cells are introduced.
Before radiation therapy or chemotherapy in cases of cancer, some of the patient's hematopoietic stem cells
are sometimes harvested and later infused back when the therapy is finished to restore the immune system.
Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are
procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or
radiation therapy. There are three types of transplants:
• In autologous transplants, patients receive their own stem cells.
• In syngeneic transplants, patients receive stem cells from their identical twin.
• In allogeneic transplants, patients receive stem cells from their brother, sister, or
parent. A person who is not related to the patient (an unrelated donor) also may be used.
One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive
very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and
PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.
Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because
cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-
dose treatments can severely damage or destroy the patient’s bone marrow. Without healthy bone marrow, the patient is
no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT
replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrow’s ability to
produce the blood cells the patient needs.
In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to
the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells
that remain in the patient’s body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them.
BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma.
To minimize potential side effects, doctors most often use transplanted stem cells that match the patient’s own stem cells
as closely as possible. People have different sets of proteins, called human leukocyte-associated (HLA) antigens, on the
surface of their cells. The set of proteins, called the HLA type, is identified by a special blood test.
How is bone marrow obtained for transplantation?
The stem cells used in BMT come from the liquid center of the bone, called the marrow. In general, the
procedure for obtaining bone marrow, which is called “harvesting,” is similar for all three types of BMTs
(autologous, syngeneic, and allogeneic). The donor is given either general anesthesia, which puts the person to
sleep during the procedure, or regional anesthesia, which causes loss of feeling below the waist. Needles are
inserted through the skin over the pelvic (hip) bone or, in rare cases, the sternum (breastbone), and into the
bone marrow to draw the marrow out of the bone. Harvesting the marrow takes about an hour.
The harvested bone marrow is then processed to remove blood and bone fragments. Harvested bone marrow
can be combined with a preservative and frozen to keep the stem cells alive until they are needed. This
technique is known as cryopreservation. Stem cells can be cryopreserved for many years.
1. How are PBSCs obtained for transplantation?
The stem cells used in PBSCT come from the bloodstream. A process called apheresis orleukapheresis is used
to obtain PBSCs for transplantation. For 4 or 5 days before apheresis, the donor may be given a medication to
increase the number of stem cells released into the bloodstream. In apheresis, blood is removed through a
large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest,
or groin area). The blood goes through a machine that removes the stem cells. The blood is then returned to the
donor and the collected cells are stored. Apheresis typically takes 4 to 6 hours. The stem cells are then frozen
until they are given to the recipient.

26. After being treated with high-dose anticancer drugs and/or radiation, the patient receives the stem cells through
an intravenous (IV) line just like a blood transfusion. This part of the transplant takes 1 to 5 hours.
The major risk of both treatments is an increased susceptibility to infection and bleeding as a result of the high-dose
cancer treatment. Doctors may give the patient antibiotics to prevent or treat infection. They may also give the
patient transfusions of platelets to prevent bleeding and red blood cells to treat anemia. Patients who undergo BMT and
PBSCT may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair
loss, and skin reactions.
Potential long-term risks include complications of the pretransplant chemotherapy and radiation therapy, such
as infertility (the inability to produce children); cataracts (clouding of the lens of the eye, which causes loss of vision);
secondary (new) cancers; and damage to the liver, kidneys,lungs, and/or heart.
With allogeneic transplants, GVHD sometimes develops when white blood cells from the donor (the graft) identify cells in
the patient’s body (the host) as foreign and attack them. The most commonly damaged organs are the skin, liver,
and intestines. This complication can develop within a few weeks of the transplant (acute GVHD) or much later (chronic
GVHD). To prevent this complication, the patient may receive medications that suppress the immune system.
Additionally, the donated stem cells can be treated to remove the white blood cells that cause GVHD in a process called
“T-cell depletion.” If GVHD develops, it can be very serious and is treated with steroids or
other immunosuppressive agents. GVHD can be difficult to treat, but some studies suggest that patients with leukemia
who develop GVHD are less likely to have the cancer come back. Clinical trials are being conducted to find ways to
prevent and treat GVHD.

27. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in
which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an
immunologic attack. It can also take place in a blood transfusion under certain circumstances.
Clinically, graft-versus-host-disease is divided into acute and chronic forms.
• The acute or fulminant form of the disease (aGVHD) is normally observed within the first 100 days
post-transplant,[2] and is a major challenge to transplants owing to associated morbidity and mortality.
[3]
• The chronic form of graft-versus-host-disease (cGVHD) normally occurs after 100 days.
Classically, acute graft-versus-host-disease is characterized by selective damage to the liver, skin and mucosa,
and the gastrointestinal tract. Newer research indicates that other graft-versus-host-disease target organs
include the immune system (the hematopoietic system—e.g. the bone marrow and the thymus) itself, and
the lungs in the form of idiopathic pneumonitis. Chronic graft-versus-host-disease also attacks the above
organs, but over its long-term course can also cause damage to the connective tissue and exocrine glands.
Acute GVHD of the GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane,
severe diarrhea, abdominal pain, nausea, and vomiting. This is typically diagnosed via intestinal biopsy. Liver
GVHD is measured by the bilirubin level in acute patients. Skin GVHD results in a diffuse maculopapular rash,
sometimes in a lacy pattern.
Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of
1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. If the GVHD is severe and
requires intense immunosuppression involving steroids and additional agents to get under control, the patient
may develop severe infections as a result of the immunosuppression and may die of infection.
Intravenously administered corticosteroids, such as prednisone, are the standard of care in acute
GVHD[13] and chronic GVHD
The Graft-versus-Tumor Effect
One of the reasons that cancer cells can grow, multiply, and spread is that the body does not recognize
them as diseased but accepts them as "self." Immune system cells transplanted from a normal donor
can often recognize cancer cells -- particularly those of leukemia patients -- as diseased cells and go to
work eliminating them. This phenomenon is called the graft-versus-leukemia or graft-versus-tumor
effect, and it is one of the reasons that allogeneic transplants can be curative.
This effect appears to be most powerful in diseases that progress slowly, like chronic leukemia,
low-grade lymphoma, and in some cases multiple myeloma, but it is less effective in the rapidly
growing acute leukemias. In some patients who relapse after transplant, the disease-killing
capability of the donor's white blood cells can be harnessed again, by infusing the patient with
more of the donor's white blood cells through donor lymphocyte infusion.

28. Febrile neutropenia is the development of fever, often with other signs of infection, in a patient
with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood.
The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well.
Fever is actually caused by infection in 50% of cases, and bacteremia (bacteria in the bloodstream) may be
present in as many as 20% of all patients with an absolute neutrophil count under 1.0.
Febrile neutropenia can develop in any form of neutropenia, but is most generally recognized as a complication
of chemotherapy when this is myelosuppressive (suppresses the bone marrow from producing blood cells).
Generally, patients with febrile neutropenia are treated with empirical antibiotics until the neutrophil count has
recovered and the fever has abated; if the neutrophil count does not improve, treatment may need to continue
for two weeks or occasionally more. Guidelines issued in 2002 by the Infectious Diseases Society of
America recommend the use of particular combinations of antibiotics in specific settings; mild low-risk cases
may be treated with a combination of oral co-amoxiclav and ciprofloxacin, while more severe cases
require cephalosporins with activity against Pseudomonas aeruginosa (e.g. cefepime),
or carbapenems(imipenem or meropenem
Sepsis is a potentially serious medical condition that is characterized by a whole-body inflammatory state
(called a systemic inflammatory response syndrome or SIRS) and the presence of a known or
suspected infection.[1][2] The body may develop this inflammatory response by the immune
system to microbes in the blood, urine, lungs, skin, or other tissues. A lay term for sepsis is blood poisoning,
more aptly applied to septicemia, below. Severe sepsis is the systemic inflammatory response, plus infection,
plus the presence of organ dysfunction.
Severe sepsis occurs when sepsis leads to organ dysfunction, such as trouble breathing, coagulation or other
blood abnormalities, decreased urine production, or altered mental status). If the organ dysfunction of severe
sepsis is low blood pressure (hypotension), or insufficient blood flow (hypoperfusion) to one or more organs
(causing, for example, lactic acidosis), this is septic shock.
Sepsis can lead to multiple organ dysfunction syndrome (MODS) (formerly known as multiple organ failure),
and death. Organ dysfunction results from local changes in blood flow, from sepsis-induced hypotension (<
90 mmHg or a reduction of ≥ 40 mmHg from baseline) and from diffuse intravascular coagulation, among other
things.
Sepsis can be defined as the body's response to an infection. An infection is caused by microorganisms or
bacteria invading the body and can be limited to a particular body region or can be widespread in the
bloodstream. Sepsis is acquired quickest with infections developed in surgery and physical contact with
someone with sepsis.
Septic shock. Defined as sepsis with refractory arterial hypotension or hypoperfusion abnormalities in spite of
adequate fluid resuscitation. Signs of systemic hypoperfusion may be either end-organ dysfunction or serum
lactate greater than 4 mmol/dL. Other signs include oliguria and altered mental status. Patients are defined as
having septic shock if they have sepsis plus hypotension after aggressive fluid resuscitation (typically upwards
of 6 liters or 40 ml/kg of crystalloid).
Leukocyte growth factors are natural molecules which are responsible for the proliferation and
differentiation of normal blood stem cells. They can nowadays be massively produced by genetic
engineering, however their cost remains high.
First generation
G-CSF (Neupogen™, Granocyte™) and GM-CSF (Leucomax™) growth factors comprised
the first generation of leukocyte growth factors. Their prescription (at least in France) was
strictly regulated.

29. It has been proven that they reduce the duration of leukopenia, but not its intensity, hence
reducing the infectious risks related to such duration.
Growth factors called colony-stimulating factors, which stimulate the production of white blood cells, are
sometimes helpful.
Bone marrow (or stem cell) transplantation is not used to treat neutropenia per se, but it may be recommended
to treat certain serious causes of neutropenia, such as aplastic anemia or leukemia.

30. Disseminated intravascular coagulation is a condition in which small blood clots develop throughout
the bloodstream, blocking small blood vessels and depleting. The increased clotting depletes the
platelets and clotting factors needed to control bleeding, causing excessive bleeding.
• There are a number of possible causes, including infection and surgery.
• Excessive clotting is followed by excessive bleeding.
• The number of clotting factors in the blood is measured.
• The underlying disorder is treated.
Disseminated intravascular coagulation (DIC) begins with excessive clotting. The excessive clotting is usually
stimulated by a substance that enters the blood as part of a disease (such as an infection or certain cancers) or
as a complication of childbirth, retention of a dead fetus, or surgery. People who have a severe head injury or
who have been bitten by a poisonous snake are also at risk. As the clotting factors and platelets are depleted,
excessive bleeding occurs.
Symptoms and Diagnosis
DIC that develops suddenly usually causes bleeding, which may be very severe. If the condition follows surgery
or childbirth, bleeding may be uncontrollable. Bleeding may occur at the site of an intravenous injection or in the
brain, digestive tract, skin, muscles, or cavities of the body.
If DIC develops more slowly, as in people with cancer, then clots in veins are more common than bleeding.
Blood tests may show that the number of platelets in a blood sample has dropped and that the blood is taking a
long time to clot. The diagnosis of DIC is confirmed if test results show diminished amounts of clotting factors
and large quantities of proteins that are produced when clots are broken up by the body (fibrin degradation
products).
Treatment
The underlying cause must be identified and corrected, whether it is an obstetric problem, an infection, or a
cancer. The clotting problems subside when the cause is corrected.
DIC that develops suddenly is life threatening and is treated as an emergency. Platelets and clotting factors are
transfused to replace those depleted and to stop bleeding. Heparin may be used to slow the clotting in people
who have more chronic, milder DIC in which clotting is more of a problem than bleeding.
Thrombocytopenia (thrombopenia in short) is the presence of relatively few platelets in blood.
Generally speaking, in human beings a normal platelet count ranges from 150,000 to 450,000 platelets per
microliter of blood.
Often, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine full blood
count (or CBC, complete blood count). Occasionally, there may be bruising, particularly purpura in the
forearms, petechia (pinpoint hemorrhages on skin and mucous membranes), nosebleeds and/or
bleeding gums.
Often occurs in Leukemia or myelodysplastic syndrome
Medication-induced
Thrombocytopenia-inducing medications include:
• Direct myelosuppression
• Valproic acid
• Methotrexate
• Carboplatin
• Interferon
• Isotretinoin

31. Infections are among the most common, potentially serious complications of cancer and its treatment.
INFECTION DURING FEBRILE NEUTROPENIA
It has long been recognized that the incidence of infection is high in patients who develop a fever during neutropenia and
that empiric antimicrobial therapy is warranted in such patients.
Neutropenia is defined as a neutrophil count of < 500/μL, although patients with a neutrophil count between 500 and
1,000/μL in whom a decrease is anticipated are considered to be neutropenic. Patients with a neutrophil count < 100/μL
are at greatest risk for infection, as are those with a rapid decrease in neutrophil count and those with protracted
neutropenia.
Bacteria Infections occurring during episodes of febrile neutropenia are caused predominantly by aerobic gram-negative
bacilli (especially Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and gram-positive cocci
(coagulase-negative staphylococci, β-hemolytic streptococci, viridans streptococci, enterococci, and Staphylococcus
aureus). In recent years, multidrug-resistant organisms have become more prominent.
Fungi Fungal infections usually occur after a patient has received broad-spectrum antimicrobial therapy and/or steroids.
The most common fungal pathogens are Candida species (predominantly C albicans and C tropicalis)
and Aspergillus species. Less common are Fusarium, Scedosporium, and Zygomycetes infections (see also section on
“Fungal infections”).
Viruses Viral infections occurring during neutropenia are caused predominantly by herpesviruses and respiratory viruses.
The herpesviruses include herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and
Epstein-Barr virus (EBV). The respiratory viruses include adenovirus, respiratory syncytial virus, parainfluenza virus,
influenza A and B viruses, metapneumovirus, and rhinovirus (see also section on “Viral infections”).
Signs and symptoms
The most remarkable aspect of the febrile, neutropenic patient is the lack of physical findings. This is due to the
neutropenia and the absence of an inflammatory response at the infection site. The patient may have only a fever with or
without chills or rigors. Even if the patient has pneumonia, there may be few respiratory symptoms. Likewise, a perirectal
abscess may be relatively asymptomatic.
Diagnosis
An initial evaluation and diagnostic work-up of any fever in a neutropenic patient should begin immediately but should not
delay the initiation of empiric therapy (see below). A complete history (exposures, past infections, rashes, cough,
abdominal pain, diarrhea) should be taken and a physical examination (skin lesions, exit site and tunnel of right atrial
catheter, oropharynx, abdomen, perineum) should be performed.
Diagnostic workup should include:
• at least two sets of blood cultures: one from a peripheral vein and one from each port of a central venous catheter. If
fever persists in the face of negative cultures, blood cultures for fungi and acid-fast bacilli should be considered.
• culture of any drainage from a catheter exit site
• stool examination for Clostridium difficile and other bacterial/protozoal agents
• urine culture and urinalysis
• chest radiograph

32. • aspiration or biopsy of any skin lesions.
CT If indicated by signs or symptoms, CT scans of the brain (followed by lumbar puncture), chest, abdomen, and pelvis
can be performed.
Laboratory tests Determination of serum transaminases, CBC, and serum creatinine is also recommended. Other
useful serologies include Aspergillus galactomannan, beta-D-glucan, Coccidioides antibody panel, and histoplasmosis
antigen, depending on the region.
Pneumocystis pneumonia (PCP) or pneumocystosis is a form of pneumonia, caused by the yeast-
like fungus (which had previously been erroneously classified as a protozoan) Pneumocystis jirovecii.
The disease PCP is relatively rare in people with normal immune systems, but common among people with
weakened immune systems
The diagnosis can be confirmed by the characteristic appearance of the chest x-ray which shows widespread
pulmonary infiltrates, and an arterial oxygen level (pO2) strikingly lower than would be expected from
symptoms. The diagnosis can be definitively confirmed by histological identification of the causative organism
in sputumor bronchio-alveolar lavage (lung rinse).
Antipyretics (literally "against the fire") are drugs that reduce fever
ibuprofen and aspirin, which are used primarily as pain relievers. Non-steroidal anti-inflammatory
drugs(NSAIDs) are antipyretic, anti-inflammatory, and pain relievers. There is some debate over the appropriate
use of such medications, as fever is part of the body's immune response to infection.

33. Pathophysiology of Nausea and Vomiting
The vomit center receives input from four major areas: the GI tract, the chemoreceptor trigger zone,
the vestibular apparatus, and the cerebral cortex. (The center also has intrinsic chemoreceptors that
can modulate, stimulate, and repress nausea.) 2,3 Each of these four areas responds to certain types
of stimuli, modulated by specific neurotransmitters that bind specific receptors. Understanding how
these areas modulate nausea and vomiting helps us tailor specific therapies for specific problems.
The GI tract
As the primary source of toxin absorption is the gut, the effect of the GI tract on the vomit center is complex.
Stimulation of the gut chemoreceptors and stretch receptors triggers nausea and vomiting via vagal nerve
afferents and afferent fibers associated with the sympathetic nervous system. Serotonin, acetylcholine,
histamine, and substance P are major neurotransmitters involved in stimulating these receptors.
Chemoreceptors in the gut appear to be major mediators of the toxic effect of certain chemotherapeutic
agents, such as cisplatin, even when such drugs are given intravenously via binding to 5HT 3 receptors. In
addition to being a neurotransmitter that stimulates nausea, acetylcholine also increases gut motility and gut
secretion. Histamine mediates transmission of nausea via the vagus nerve. Substance P binds neurokinin 1
receptors in the gut (and directly in the vomit center in the brain). 4,5
The chemoreceptor trigger zone (CTZ)
The CTZ senses chemicals in the blood. The CTZ is particularly sensitive to increasing blood levels of
potentially toxic substances. If a toxic substance is detected, nausea is experienced and the vomit reflex
initiated - hopefully before more toxin is absorbed. It is easy to understand the evolutionary advantage of
such a failsafe. The brain detects an "alien" chemical. By itself, this is not so unusual - we have lots of
peculiar non-self chemicals floating around in our bloodstreams. However, if the concentration of a chemical
is rapidly rising, this could constitute a threat to our health - better to expel any residual substance in the
stomach; better safe than dead. Two major neurotransmitters are involved - dopamine, acting on
D2 receptors, and serotonin, acting on 5HT 3 receptors. Different toxin responses are mediated through
different neurotransmitters. Opioid-related nausea appears to be most related to stimulation of D 2 receptors.
Understanding this has helped with selective blockage of specific receptors in specific disorders.
The vestibular apparatus
Motion and body position are sensed through the vestibular apparatus. Motion sickness, such as car
sickness and seasickness, are mediated through the vestibular apparatus, as are inner-ear diseases, such
as Meniere's disease. The vestibular apparatus may once have served as a sensor for certain neurotoxins
(such as alcohol) that can produce disequilibrium. Stimulation of the vestibular apparatus by alcohol may
provide a survival advantage in keeping our species from, literally, drinking ourselves to death. Stimulus of
the vestibular apparatus is mediated largely through histamine and acetylcholine receptors.
The cerebral cortex
The cerebral cortex and associated structures in the limbic system modulate complex experiences such as
taste, sight, and smell as well as memory (involved in anticipatory nausea) and emotion. Discrete
neuropathways are less well understood. However, higher cortical effects are still important and can be
extremely powerful in stimulating and suppressing nausea and vomiting.
Chemotherapy-induced nausea and vomiting can be broadly categorized as acute
(occurring within 24 hours of therapy), delayed (persisting for 6–7 days after therapy), or
anticipatory (occurring prior to chemotherapy administration). Breakthrough and refractory
nausea and vomiting describe the symptoms of uncontrolled emesis.
The 5-HT3-receptor antagonists, regarded as the ‘gold standard’ in antiemetic therapy, are the
first-line treatment for moderately and highly emetogenic chemotherapy

34. A class of drugs called 5-HT3 antagonists are the most effective antiemetics and constitute the single greatest
advance in the management of nausea and vomiting in patients with cancer. These drugs block one or more of
the nerve signals that cause nausea and vomiting. During the first 24 hours after chemotherapy, the most
effective approach appears to be blocking the 5-HT3 nerve signal. Approved 5-HT3 inhibitors
includedolasetron, granisetron, and ondansetron (Zofran). The newest 5-HT3 inhibitor, palonosetron, also
prevents delayed nausea and vomiting, which occurs during the 2–5 days after treatment. Since some patients
have trouble swallowing pills, these drugs are often available by injection, as orally disintegrating tablets, or
as transdermal patchs.

35. Mucositis is a medical term that is used to refer to mouth sores, oral mucositis, or esophagitis. It can range in severity
from a red, sore mouth and/or gums to open sores that can cause a patient to be unable to eat. The lining of the entire
gastrointestinal tract (mouth, throat, stomach, and bowel) is made up of epithelial cells, which divide and replicate rapidly.
Imagine this: if you bite your lip, the tissue is often able to heal by the next day because of this rapid growth.
Chemotherapy and radiation therapy kill not only cancer cells, but other rapidly dividing cells as well, including the lining
of the entire gastrointestinal tract. This article will discuss the effects on the lining of the mouth and throat (this lining is
called the mucosa).
Oral mucositis leads to several problems, including pain, nutritional problems as a result of inability to eat, and
increased risk of infection due to open sores in the mucosa. It has a significant effect on the patientÕs quality of
life and can be dose- limiting (requiring a reduction in subsequent chemotherapy doses).
Signs and symptoms of mucositis include:
 Red, shiny, or swollen mouth and gums
 Blood in the mouth
 Sores in the mouth or on the gums or tongue
 Soreness or pain in the mouth or throat
 Difficulty swallowing or talking
 Feeling of dryness, mild burning, or pain when eating food
 Soft, whitish patches or pus in the mouth or on the tongue
 Increased mucus or thicker saliva in the mouth
Who gets mucositis?
Over forty percent of patients who receive chemotherapy will develop some degree of mucositis during the course
of their treatment. Patients receiving radiation to the head, neck, or chest areas, and patients who undergo bone
marrow or stem cell transplant, are even more likely to develop mucositis. Certain chemotherapy agents are more
likely to cause this side effect (Table 1), as is total body irradiation, often used for bone marrow transplants.
Table 1: Chemotherapy agents known to cause mucositis
Alemtuzumab (Campath) Bleomycin (Blenoxane) Asparaginase (Elspar)
Cyclophosphamide Cytarabine (Cytosar-U) Busulfan (Myleran,
(Cytoxan) Busulfex)
Docetaxel (Taxotere) Doxorubicin Capecitabine (Xeloda)
(Adriamycin)
Fluorouracil (5-FU) Gemcitabine (Gemzar) Carboplatin
(Paraplatin)
Gemtuzumab ozogamicin Hydroxyurea (Hydrea) Daunorubicin
(Mylotarg) (Cerubidine)
Idarubicin (Idamycin) Interleukin 2 Epirubicin (Ellence)
(Proleukin)
Lomustine (CeeNU) Melphalan (Alkeran) Etoposide (VePesid)
Mitomycin (Mutamycin) Mitoxantrone Irinotecan
(Novantrone) (Camptosar)
Oxaliplatin (Eloxatin) Paclitaxel (Taxol) Methotrexate
(Rheumatrex)
Pentostatin (Nipent) Procarbazine Mechlorethamine
(Matulane) (Mustargen)
Topotecan (Hycamtin) Trastuzumab Pemetrexed (Alimta)
(Herceptin)
Vinblastine (Velban) Vincristine (Oncovin) Thiotepa (Thioplex)
Tretinoin (Vesanoid)
Chemotherapy often causes hair loss otherwise known as Alopecia. This is because the cells in the hair follicles
grow fast and chemotherapy damages fast growing cells. (see what is chemotherapy). Hair loss is not permanent
and it will grow back once your treatment has ended. Not all drugs cause hair loss - Some just cause thinning and

36. others cause dramatic hair loss including the body hair and eye brows. Furthermore, different people have
different tolerances to the drugs.

37. Malnutrition:
The World Health Organization defines malnutrition as "the cellular imbalance between supply of nutrients and
energy and the body's demand for them to ensure growth, maintenance, and specific functions.
In severe cases, malnutrition can progress to cachexia, a specific form of malnutrition characterised by loss of lean body
mass, muscle wasting, and impaired immune, physical and mental function. Cancer cachexia is also associated with
poor response to therapy, increased susceptibility to treatment-related adverse events, as well as poor outcome and
quality of life.
Indications for nutritional support:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1434612/?page=1
A feeding tube is a medical device used to provide nutrition to patients who cannot obtain nutrition by
swallowing.
asogastric
A nasogastric feeding tube, or "NG-tube", is passed through the nares (nostril), down the esophagus and into
the stomach.
[edit]Gastric feeding tube
A gastric feeding tube (or "G-tube," or "button") is a tube inserted through a small incision in the abdomen into
the stomach and is used for long-term enteral nutrition. One type is the percutaneous endoscopic
gastrostomy (PEG) tube. It is placed endoscopically: the patient is sedated and an endoscope is passed
through the mouth and esophagus into the stomach. The position of the endoscope can be visualized on the
outside of the patient's abdomen because it contains a powerful light source. A needle is inserted through the
abdomen, visualized within the stomach by the endoscope, and a suture passed through the needle is grasped
by the endoscope and pulled up through the esophagus. The suture is then tied to the end of the PEG tube that
will be external, and pulled back down through the esophagus, stomach, and out through the abdominal wall.
The insertion takes about 20 minutes. The tube is kept within the stomach either by a balloon on its tip (which
can be deflated) or by a retention dome which is wider than the tract of the tube.
Gastric tubes are suitable for long-term use; they last about six months, and can be replaced through an
existing passage without an additional endoscopic procedure. The G-tube is useful where there is difficulty with
swallowing because of neurologic or anatomic disorders (stroke, esophageal atresia, tracheoesophageal
fistula), and to avoid the risk of aspiration pneumonia. It is also used when patients are malnourished and
cannot take enough food by mouth to maintain their weight, such as with mitochondrial disease and short bowel
syndrome.
Feed preparations
Various nutritionally complete pre-packaged feeds are available:
• Standard enteral feeds:
• These contain all the carbohydrate, protein, fat, water, electrolytes, micronutrients
(vitamins and trace elements) and fibre required by a stable patient.
• "Pre-digested" feeds:
• These contain nitrogen as short peptides or free amino acids and aim to improve nutrient
absorption in the presence of pancreatic insufficiency or inflammatory bowel disease.
• The fibre content of feeds is variable and some are supplemented with vitamin K, which may
interact with other medications.

38. Parenteral nutrition (PN) is feeding a person intravenously, bypassing the usual process
of eating and digestion. The person receives nutritional formulas that contain nutrients such
as salts, glucose, amino acids, lipids and added vitamins. It is called total parenteral nutrition or total
nutrient admixture (TPN or TNA) when no food is given by other routes.
Parenteral nutrition is indicated to prevent the adverse effects of malnutrition in patients who are unable to
obtain adequate nutrients by oral or enteral routes. Other indications are short gut syndrome, high-output
fistula, prolonged ileus, or bowel obstruction.
The nutrient solution consists of water and electrolytes; glucose, amino acids, and lipids; essential vitamins,
minerals and trace elements are added or given separately. Previously lipid emulsions were given separately
but it is becoming more common for a "three-in-one" solution of glucose, proteins, and lipids to be administered
The preferred method of delivering PN is with a medical infusion pump. A sterile bag of nutrient solution,
between 500 mL and 4 L, is provided. The pump infuses a small amount (0.1 to 10 mL/hr) continuously in order
to keep the vein open. Feeding schedules vary, but one common regimen ramps up the nutrition over one hour,
levels off the rate for a few hours, and then ramps it down over a final hour, in order to simulate a normal
metabolic response resembling meal time. This should be done over 12 to 24 hours rather than intermittently
during the day.
Chronic PN is performed through a central intravenous catheter, usually through the subclavian or jugular
vein with the tip of the catheter at the superior vena cava without entering the right atrium. Another common
practice is to use a PICC line, which originates in the arm, and extends to one of the central veins, such as the
subclavian with the tip in the superior vena cava.

39. Organ toxicity of oncological therapy:
Cardiotoxicity:
The anthracyclines are perhaps the most notorious offenders. Acute reactions include chest discomfort and shortness of
breath consistent with a myopericarditis. Toxicity can also develop months after the last chemotherapy dose and typically
presents as new onset heart failure with left ventricular systolic dysfunction. Late reactions are seen years after
presentation as new-onset cardiomyopathy, often in patients who were treated for childhood neoplasms. 5-Fluorouracil,
its prodrug capecitabine, and trastuzumab, a tumor-specific antibody, have also been associated with cardiotoxicity.
Nephrotoxicity is one of the most common kidney problems and occurs when your body is
exposed to a drug or toxin that causes damage to your kidneys. When kidney damage occurs,
you are unable to rid your body of excess urine, and wastes. Your blood electrolytes (such as
potassium, and magnesium) will all become elevated.
Nephrotoxicity can be temporary with a temporary elevation of lab values (BUN and/or creatinine). If these
levels are elevated, these may be due to a temporary condition such as dehydration or you may be developing
renal (kidney failure). If the cause of the increased BUN and/or creatinine levels is determined early, and your
healthcare provider implements the appropriate intervention, permanent kidney problems may be avoided.
Chemotherapy drugs such as: Cisplatin, Carboplatin, Carmustine, Mitomycin, high-dose Methotrexate.
• Biologic therapy such as Interleukin-2, or Interferon Alfa.
Hepatotoxicty
Toxic liver injury can reproduce virtually any known pattern of injury, including necrosis,
steatosis, fibrosis, cholestasis, and vascular injury
Alkylating agents e.g. chlorambucil, cyclophosphamide
Antimetabolites: 6-mercaptopurine (6-MP), methotrexate.
The antitumor antibiotics include doxorubicin, daunorubicin, mitoxantrone, bleomycin,
mitomycin, mithramycin (plicamycin),and dactinomycin.
Neurotoxicity
Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy.
Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with
growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the
risk of neurotoxicity. Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral
neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even
coma. In this article we describe the neurological adverse effects of the most commonly used chemotherapeutic agents.
The vinca-alkaloids, cisplatin and the taxanes are amongst the most important drugs inducing peripheral neurotoxicity.
These drugs are widely used for various malignancies such as ovarian and breast cancer, and haematological cancers.
Chemotherapy-induced neuropathy is clearly related to cumulative dose or dose-intensities. Patients who already have
neuropathic symptoms due to diabetes mellitus, hereditary neuropathies or earlier treatment with neurotoxic
chemotherapy are thought to be more vulnerable for the development of chemotherapy-induced peripheral neuropathy.
Methotrexate, cytarabine (cytosine arabinoside) and ifosfamide are primarily known for their central neurotoxic side
effects. Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising
cognitive deficits, hemiparesis, aphasia and progressive dementia.
Pulmonary toxicity:
Pulmonary (lung) toxicity occurs when you are exposed to a chemical or an agent that causes
damage to your lungs. You may develop a mild or severe form of pulmonary toxicity. Pulmonary
toxicity may be described as:
• A form of lung fibrosis or pneumonitis (inflammation of the lung)
• A form of non-heart related pulmonary edema (swelling in your lungs)

40. • A sudden onset or occurrence of being overly sensitive (hypersensitive) to your chemotherapy or radiation
therapy
Antitumor antibiotics - Such as bleomycin and mitomycin are the most common drugs that
cause pulmonary toxicity. Your risk may increase if you are over 70 years of age, and had prior
radiation to your chest area.
• Antimetabolites- such as methotrexate - have been known to cause pulmonary toxicity.
• Alkylating agents - such as busulfan have been known to cause pulmonary toxicity
• Nitrosoureas - such as BCNU or carmustine have been known to cause pulmonary toxicity
• Vinca Alkaloids - such as vincristine sulfate - may cause pulmonary toxicity if used in combination with
mitomycin