The document discusses various types of anticancer drugs including alkylating agents like cisplatin and cyclophosphamide, antimetabolites like methotrexate and 5-fluorouracil, and targeted drugs. It describes their mechanisms of action, toxicities, and common uses in treating cancers like breast cancer, leukemia, lymphoma, and others. The goal of cancer chemotherapy is to cure cancer when possible or induce remission, but the drugs can also be used for palliation to reduce tumor size and prolong life when the cancer is not curable.

1. Anticancer Drugs
DR. D. K. BRAHMA
ASSOCIATE PROFESSOR
DEPARTMENT OF PHARMACOLOGY
NEIGRIHMS, SHILLONG

2. Introduction
The anticancer drugs either kill cancer cells or modify their growth – but, selectivity of these
drugs limited – damages normal cells too …..
TOXICITY

3. Introduction
No Treatment: Before 1940 (Nitrogen mustard)
◦Rapid progress since then
Surgery: before 1955
Radiotherapy: 1955 - 1965
Chemotherapy: after 1965
Immunotherapy, Hormone therapy , stem cell transplant and Gene therapy
Innovations: Target growth factors, specific signaling pathways, angiogenesis
and tumour antigen etc.

4. Aims of Therapy
Cure or induce prolonged ‘remission’ so that all macroscopic and microscopic
features of the cancer disappear, though disease is known to persist - Acute
Lymphoblastic Leukaemia, Wilm`s tumor, Ewing`s sarcoma, Retinoblastoma and
Rhabdomyosarcome etc. in children
◦ Hodgkin`s lymphoma, testicular teratoma, seminoma and choriocarcinoma etc.
Palliation: Shrinkage of evident tumour, alleviation of symptoms and
prolongation of life - Breast cancer, ovarian cancer, endometrial carcinoma, CLL,
CML, small cell cancer of lungs and Non-Hodgkin lymphoma
◦Insensitive or less sensitive but life may or may not be prolonged - Cancer esophagus, cancer
stomach, sq. cell carcinoma of lung, melanoma, pancreatic cancer, myeloma, colorectal
cancer

5. Aim of Therapy – contd.
Adjuvant therapy: One of the main basis of treatment now
◦ For mopping up of residual cancer cells including metastases after Surgery, Radiation and
immunotherapy etc.
Routinely used now
Mainly in solid tumours – combined modality approach

6. Cancer Chemotherapy – 5 years
survival rate
Childhood Acute Lymphoblastic
Leukemia
50 - 80%
Acute Adult Lymphoblastic Leukemia 20 - 60%
Childhood Acute Myeloblastic
Leukemia
20 - 60%
Adult Acute Myeloblastic Leukemia 10 - 20%
Breast Cancer 5 - 20%
Hodgkin’s lymphoma 40 - 80%

7. General Toxicities
Harmful to normal tissues – rapidly multiplying cells (drug targets – nucleic acid synthesis) -
particularly to GI mucosa, Bone marrow, RE system and gonads and hair cells
Steep dose response curve
Low therapeutic index
Effects are in dose dependent manner

8. Toxicities – Immunity and Infections
Bone marrow depression (at therapeutic doses): Agranulocytopenia,
agranulocytosis, thrombocytopenia and aplastic anaemia etc. –
Infection and Bleeding - often limits treatment
Lymphoreticular system: Lymphocytopenia and inhibition of
lymphocyte function – suppression of CMI and humoral immunity
◦Epithelial damage + above 2 - - susceptibility to infections
◦Fungi – Candida; Viruses – Herpes zoster and CMV; Toxoplasma and
Pneumocystis jiroveci

9. Toxicities of anticancer – contd.
•Oral cavity: Buccal mucosa - High epithelial turnover - stomatitis
• Regular minor trauma to oral mucosa and gums + presence of high oral microflora + lowered immunity
– increased oral infections
• Xerostomia – dental carries
• Bleeding of gums
•GIT: Diarrhoea, shedding of mucosa, haemorrhage – decrease in rate of renewal
• Nausea, vomiting – CTZ direct stimulation and generation of emetic impulses/mediator from Upper GIT
•Skin: alopecia
•Gonads: oligospermia, impotence, amenorrhea and infertility
•Foetus: Abortion, fetal death and teratogenicity

10. Toxicities of anticancer – contd.
Carcinogenicity: leukaemias and lymphomas
Hyperuricaemia: Uric acid- Purine metabolism - Acute renal failure, gout and lithiasis
Specific toxicities: Neuropathy, myopathy, cystitis, alopecia etc.

11. Anticancer Drugs

12. Classification

According to chemical structure and sources of drugs:
◦ Alkylating Agents, Antimetabolite, Antibiotics, Plant Extracts, Hormones and Others

According to biochemical mechanisms of anticancer action:
◦ Block nucleic acid biosynthesis
◦ Direct influence the structure and function of DNA
◦ Interfere transcription and block RNA synthesis
◦ Interfere protein synthesis and function
◦ Influence hormone homeostasis
According to the cycle or phase specificity of the drug:
◦ Cell cycle nonspecific agents (CCNSA) & Cell cycle specific agents (CCSA)
However – They may overall act as Cytotoxic (directly nonspecific action on cells) or at specific target or Indirectly via Hormone

13. Drugs acting directly on cells (cytotoxic
drugs)
Alkylating Agent:
◦ Nitrogen mustards: mechlorethamine, cyclophosphamide, ifosfamide, chlorambucil, Mephalan
◦ Ethylenimine: Thio-TEPA
◦ Alkyl sulfonate: Busulfan
◦ Nitrosoureas: Carmustine, Lomustine
◦ Triazine: Dacarbazine, Tremozolomide
◦ Methylhadrazine: Procarbazine
◦ Platinum: cis-platinium, carboplatin and Oxaliplatin
Antimetabolites:
◦ Folate antagonist: Methotrexate (Mtx), Penetrexed
◦ Purine antagonist: 6-Mercaptopurine (6-MP) and 6-Thioguanine (6-TG)
◦ Pyrimidine antagonist: 5-Fluorouracil and cytarabine

14. Cytotoxic Drugs – contd.
Antitubulins: vinca alkaloids (vincristine and vinblastin) and taxanes (paclitaxel and
docetaxel), Estramustine (Bind tubulin, destroy spindle to produce mitotic arrest)
Topoismerase-2 inhibitor: Etoposide
Topoismerase-1 inhibitor: Topotecan and Irinotecan
Antibiotic: Bleomycin, Mitomycin C, Actinomycin D (dactinomycin), Doxorubicin,
Daunorubicin, Epirubicin, Mitoxantrone
Miscellaneous: Hydroxyurea, L-asparginase, Tretinoin, Arsenic trioxide

15. Targetted Drugs
Tyrosine protein kinase inhibitor: Imatinib, Nilotinib
EGF receptor inhibitors: Geftinib, Erlotinib, Cetuximab
Angiogenesis inhibitors: Bevacizumab, Sunitinib
Progesterone inhibitors: Bortezomib
Unnamed monoclonal antibody: Rituximab, Trastuzumab

16. Influence hormone homeostasis
These drugs bind to hormone receptors to block the actions of hormones which results in
inhibition of tumor growth
Glucocorticoid drug: prednisolone and others
Estrogens and estrogen receptor modulators: (EE, fosfestrol, SERM-tamoxifene, Toremifene)
◦ Estrogen receptor down regulators: Fulvestrant
Aromatase inhibitor: Letrozole and anastrazole, Exemestane
Androgen antagonists: Flutamide and Bicalutamide)
Progestogen drug: Hydroxyprogesterone acetate
GnRH inhibitor: Nafarelin, Triptorelin, Leuprorelin
5- reductase inhibitors:ɑ Finasteride, Dutasteride

17. Individual anticancer
drugs

18. Alkylating agents
Highly reactive carbonium ion intermediate – transfer alkyl group to cellular
macromolecules
Position 7 of guanine residues – others also (carboxyl, hydroxyl etc.)
Results in cross linking/abnormal base pairing/scission of DNA strands
Also cross linking of nucleic acid with proteins
Radiomimetic actions – like ionizing radiation
Non specific action on cell stages
Some – CNS stimulant and cholinergic properties

19. Drugs PA MOA ADRs Uses
Mechlorethamine Highly reactive, local
vescicant -
Nausea, vomiting, extravasations - sloughing HL, NHL - MOPP
Cyclophosphamide No local effect – popular
and wide range of action
Active metabolite –
aldophosphamide,
phosphoramide mustard,
Immunosuppressant
Alopecia and cystitis (acrolein) and emetogenic
Chloramphenicol retards metabolism
Solid tumours
Isofosfamide Congener of Cycloph –
longer t1/2
- Haemorrhagic cystitis (mesna is –SH compound),
lesser emetogenic
Broncogenic CA, breast, testicular,
bladder, head & neck, osteogenic
sarcoma
Clorambucil Slow acting – for lymphoid
tissue, not myeloid
Immunosuppressant DOC - Chronic lymphatic leukaemia,
NHL and few solid tumours
Mephalan BM depression, Infection, Diarrhoea, pancreatitis Multiple myeloma
Busulfan For myeolid tissue, not
lymphoid
Hyperuricaemia, pulmonary fibrosis and skin
pigmentation
DOC in CML
Nitrosoureas Highly lipid soluble – wide
range of activity, cross BBB
CNS action – nausea, vomiting, BM depression (6
weeks) …. Visceral fibrosis and renal damage
Meningeal leukaemias, brain cancer
Dacarbazine Activated in liver, methylates
DNA
Nausea, vomiting, flu like symptoms, neuropathy
and myelosuppression
Malignant melanoma, HL
Procarbazine Not classical agent Activated in liver, methylates
and depolymerizes DNA, also
inhibition of nucleic acid
synthesis
Mutagenic and carcinogenic, Male sterility,
vomiting, leucopenia, thrombocytopenia …Weak
MAO inhibitor – sedation, disulfiram reaction with
alcohol
MOPP regimen – HL and for brain
tumours

20. Platinum compounds – cisplatin,
carboplatin, oxaliplatin
Hydrolyzed intracellularly to a highly reactive moiety – causes cross linking of DNA (CTR1 and MRP1)
N7 of guanine residues
Also reacts with –SH of cytoplasm and nuclear proteins
Effects resemble alkylating agents and radiation
Penetrate tissues and excreted slowly unchanged in urine
T1/2 = 72 hours
Uses: Metastatic testicular and ovarian tumours – also in lung, bladder, esophageal, hepatic, gastric etc.
solid tumours
ADRs: Highly emetic, renal impairment – hydration required; also ototoxic and neurotoxic
Carboplatin – 2nd
generation and oxaliplatin – 3rd
generation

21. Antimetabolites
Folic acid Antagonists: MTX
Purine Antagonists: 6MP and 6-TG
Pyrimidine Antagonists: 5-FU and Cytarabine
General Characteristics:
Antimetabolites are S phase-specific drugs that are structural analogues of
essential metabolites and that interfere with DNA synthesis
Myelosuppression is the dose-limiting toxicity for all drugs in this class

22. Methotrexate – Folate Antagonist
MOA:
◦ The structures of MTX and folic acid are similar
◦ MTX is actively transported into mammalian cells and inhibits dihydrofolate reductase
◦ Enters cell by Folate carrier – converts to more active polyglutamate form (FPGS)
◦ the enzyme that normally converts dietary folate to the tetrahydrofolate required for one carbon atom transfer
reactions in de novo purine synthesis and amino acid interconversion
◦ Enzyme inhibition – pseudoirreversible (although 50,000 times higher affinity than normal substrate)
◦ Additionally, also inhibits thymidylate synthase – DNA synthesis inhibition – RNA and protein also suffers
◦ Low doses – bone marrow toxicity, megaloblastic anaemia; high doses – pancytopenia
◦ Mucositis, diarrhoea and desquamation and bleeding
Leucovorin rescue (folinic acid rescue):
◦ Administered as a plan in MTX therapy
◦ Leucovorin (Folinic acid) is directly converted to tetrahydrofolic acid - production of DNA cellular protein in spite of
presence of MTX
◦ Used to rescue bone marrow and GIT mucosal cells
◦ Permits higher doses

23. Methotrexate – contd.
Kinetics:
◦ Given orally/IM /IV and also intrathecally and good oral absorption
◦ Little metabolized, excreted unchanged in urine
◦ CSF entry - intrathecal
Indications:
◦ Choriocarinoma - was the first demonstration of curative chemotherapy – 15 – 30 mg/day for 5 days
◦ Maintenance of remission of Acute lymphatic leukemia in children but not good for inducing remission
◦ Tumors of head and neck, NHL, breast and bladder cancers
◦ Meningeal metastases of a wide range of tumors
Resistance: Reduction of affinity of DHFR to MTX, diminished entry of MTX into cancer cells and over production
of DHFR enzyme
Permetrexed: Newer congener of Mtx – targets thymidylate synthase - less interference with DHFRase;
hand foot syndrome

24. Purine Antagonists – 6MP, 6TG and
Azathioprine (AZA)
Highly effective: antineoplastic – also primarily used as immunosuppressant in Rh arthritis and organ transplantation
MOA: 6-MP and 6-TG - Converted to corresponding monoribonucleotides – inhibits conversion of inosine
monophosphate to adenine and guanine nucleotides …also feedback inhibition of de novo purine synthesis
• Get incorporated to RNA and DNA
Kinetics: AZA and -MP - Metabolized by xanthine oxidase (inhibited by allopurinol) and allopurinol dose has to be
adjusted to ½ or 1/4th
◦ 6-TG is also metabolized by s- methylation
◦ 6-MP also metabolized by methylation by thiopurine methyl transferase ((TPMT) – genetic deficiency of TPMT –
toxicity
◦ Over expression of TPMT – resistance to 6-MP
◦ Toxicity of Azth – enhanced due to TPMT deficiency
ADRs: all cause BM depression, nausea vomiting with 6-MP, reversible jaundice and hyperuricaemia
Uses: Childhood acute leukaemia, choriocarcinoma, solid tumours , both to induce remission and 6-MP to maintain
Azathioprine : prodrug – converts to 6-MP (prominent immunosuppressant action)

25. Antimetabolites (Pyrimidine Antagonists) - 5
FU
Pyrimidine antagoists – antineoplastic, antifungal and antipsoriatic
MOA: 5- FU
◦Fluorouracil is an analogue of thymidine
◦Converted to corresponding nucleotide - 5-fluoro-2deoxy-uridine monophosphate (5-
FdUMP) – forms covalent ternary complex with methyl-THFA and thymidylate synthase (TS) –
irreversible inhibition of TS
◦Blocks conversion of deoxyuridilic acid to deoxythymidylic acid – failure of DNA synthesis due
to noavailability of thymidylate
◦Thymidine can partially reverse 5-FU toxicity
◦2nd
mechanism: 5-FU itself gets incorporated to RNA – interferes RNA synthesis
◦Concurrent administration of Leucovorin (5-FU action depends on THFA) – enhances 5-FU
action
◦Cisplatin and oxaliplatin synergizes 5-FU action

26. 5 FU – contd.
Kinetics: Used IV – metabolized by dihydropyrimidine dehydrogenase (DPD) – plasma half-life –
15-20 minutes
◦ Genetic deficiency of DPD – severe 5-FU toxicity
ADRs: BM and GIT myelosuppression - mucositis, diarrhoea, nausea, vomiting and peripheral
neuropathy
Uses: Solid malignancies – especially colon, rectum, stomach, pancreas, liver, urinary bladder
and Head & Neck

27. Antitubulins
Vinca alkaloids (Vinca rosea or Catharanthus roseus) Taxanes – Western yew tree
Binds to microtubular protein – tubulin – prevents its
polymerization – cause disruption of mitotic spindle and
interfere with cytoskeletal function
Chromosomes fail to move apart during mitosis –
metaphase arrest
Binds to β-tubulin and enhances its polymerization –
microtubules are stabilized and depolymerization is
prevented
Stability results in inhibition of normal dynamic
reorganization of the microtubule network for interphase
and mitoticfunction - Abnormal microtubules are formed
Vincristine – remission of childhood acute lymphoblastic
leukaemia
Also AML, WT, HD
ADR: Neuropathy and alopecia; also paralytic ileus,
postural hypotension, urinary retention
Paclitaxel – Metastatic ovarian and breast carcinoma – after
failure of 1st
line therapy
Also in small cell lung cancer, esophageal adenocarcinoma
etc.
Myelosupression and “stocking and gloves” neuropathy
Vinblastin – With other drugs in HD, Kaposi sarcoma, NHL,
breast and testicular cancer

28. Topoisomerase 1 and 2 inhibitors
Etoposide: Topoisomerase-2 inhibitor – causes DNA breaks by affecting DNA Topoisomerase-2
function (G2 Phase) – testicular and lung cancers
Topotecan, Irinotecan: Similar to etoposide but acts on Topoisomerase – 1 – used in metastatic
carcinoma of ovary and lung cancer

29. Antibiotics – Actinomycin D,
Daunorubicin etc.
Actinomycin D (Dactinomycin): Potent
antineoplastic
Highly effective in Wilm`s Tumour and
chilodhood rhabdomyosarcoma
Also in Mtx resistant choriocarcinoma, Ewing`s
sarcoma, metastatic testicular carcinoma
MOA: Blocking of RNA transcription by
interfering with template function of DNA –
also single strand break in DNA (dactinomycin)
ADRs: Vomiting, stomatitis, diarrhoea,
erythema, desquamation of skin
Daunorubicin: Limited to acute myeloid and
lymphoblastic leukaemia
Doxorubicin: Also effective in many solid
tumours – breast, lung, sarcoma, thyroid,
ovary, bladder
MOA: Intercalate between DNA strands –
block DNA and RNA synthesis; also strand
breakage of DNA
Toxicity: Cardiotoxicity – arrhythmia and
hypotension – ECG; also CHF
Also mutagenic and carcinogenic

30. Miscellaneous
Hydroxyurea: Inhibits ribonucleoside diphosphate reductase – so blocks
conversion of ribonucleotides to deoxyribonucleotide (S specific action)
Well absorbed orally – t1/2 – 4 hours
Uses: CML, Polycythaemia vera
◦Important use: Radiosensitizer prior to radiotherapy and 1st
line drug in sickle
cell disease in adults
ADRs: Myelosupression, GIT disturbance and cutaneous reactions

31. L-asparginase (L-ASPase)
Leukaemic cells are deficient in L-aspargine synthase enzyme – takes L-aspargine from surrounding
medium
◦ L-ASPase obtained from E. coli – degrades L-aspargine to L-aspartic acid – deprive leukaemic cells – cause cell
death
Used in Acute lymphoblastic leukaemia – for inducing remission with Mtx, prednisolone, vincristine
Drawbacks: Resistance – leukaemic cells develop L-aspargine synthase + produce antibodies which can
inactivate and clears the enzyme rapidly
Peg-asparginase – a polyethylene glycol L-ASPase - slow and long acting
ADR: atypical ADRs – due to defective protein synthesis – hyperglycaemia, raised triglycerides, liver
damage, clotting defects, allergic reactions urticaria and anaphylaxis

32. General Principles of Chemotherapy of
Cancer
1. Analogous with Bacterial chemotherapy – differences are
◦ Bacterial metabolism differs from host – but malignant cells not much different - Selectivity of drugs is limited –
because “I may harm you” – lately - (antigens, oncogenes – CML tyrosine protein kinase gene)
◦ Microorganisms are amenable to immunological and other host mechanism; Interferon, Interleukins, TNF etc.
1. A single clonogenic malignant cell can produce progeny – kill host. All malignant cells must be killed or removed
2. Subpopulation cells differ in rate of proliferation and susceptibility to chemotherapy – 1st
order kinetics – certain
fractions of cells are killed
3. Drug regimens or combined cycle therapy to minute residual tumour cells after radiation or surgery – effectively
palliate large tumour burden (Basis of treatment now) – combined modality
4. Complete remission should be the goal – used in maximum tolerated dose
5. Formerly one drug – now 2-5 drugs in intermittent pulses - Total tumour cell kill – recovery time for normal cells
in between

33. Combination chemotherapy
- synergistic
Drugs which are effective when used alone
Drugs with different mechanism of action
Drugs with differing toxicities
Drugs with different mechanism of toxicities
Drugs with synergistic biochemical interactions
Optimal schedule by trial and error method
Kinetic scheduling: on the basis of cell cycle specificity (CCS)/non specificity
(CCNS)

34. Cell Cycle and Clinical Importance
• Malignant cells spend time in each phase - longest
time at G1, but may vary
• Many of the effective anticancer drugs exert their
action on cells traversing the cell cycle - cell cycle-
specific (CCS) drugs
• Cell cycle-nonspecific (CCNS) drugs - sterilize
tumor cells whether they are cycling or resting in the
G0 compartment
• CCS are more effective on cycling cells – generally in
S-phase; but may be others also

35. Drugs Based on Cell Cycle
CCNS: Nitrogen Mustards, Cyclphosphamide, chlorambucil, carmustine,
dacarbazine, busulfan, L-asparginase, cisplatin, procarbazine and
actinomycine D etc.
CCS:
◦G1 – vincristine
◦S – Mtx, cytarabine, 6-thioguanine, 6-MP, 5-FU, daunorubicin, doxorubicin
◦G2 – Daunorubicin, bleomycin
◦M – Vincristine, vinblastne, paclitaxel etc.

36. Cell cycle and clinical importance – contd.
CCS drugs are given in short courses (pulses) – non-cycling cells can
reenter in between
CCS drugs are scheduled after a course of CCNS drugs
CCS – effective against hematologic malignancies and in solid tumors
with large growth fraction
CCNS drugs – solid tumors with low growth fraction solid tumors

37. The MOPP and Ewing`s Sarcoma
Regimes in Hodgkin's

38. The Log kill Hypothesis
One round of chemotherapy does not kill all the cells in a tumour – unlike
antimicrobials
Relationship of tumor cell number to time of diagnosis, symptoms, treatment and
survival – expressed as logarithmic function (log kill)
Cell kill hypothesis: actions of CCS drugs follow first order kinetics: a given dose kills a
constant PROPORTION of a tumor cell population (rather than a constant NUMBER of
cells) – leukaemias and lymphomas
Therefore, magnitude of a tumor cell kill is a logarithmic function: 4 log kill means
reduction of tumour cells from1012
to 108

39. The Neoplastic
Cell Burden – Log kill
May have up to 1012
tumor cells throughout
the body at the time of death
109
(100 crore) cells at the time of diagnosis
Debulking – 90% done
Still 10% left i.e. 109
became108
or 10 crores
(log kill is 9-8 = 1)
There would still be up to 8 logs of tumor cells
◦Inherent resistance to drug,
Pharmacological sanctuary (CNS and
testes), G(0) cycle
100,0000000 (109
)
90% Debulked
10% remaining = 100000000 (108
)
Log kill = 109
- 108
= 1
LOG KILL 1 (ONE) IS NOT SUFFICIENT

40. The Neoplastic
Cell Burden – Log kill
An effective drug combination is capable of
killing 99.999% tumor cells - clinical remission
and symptomatic improvement (log kill 5) -
Still 0.001% cells
In common bacterial infections – host defense
mechanism would take care
However, in cancer, single clonogenic
malignant cell – produce progeny kill host cells
Therefore, early treatment, continuation
beyond zero cell diagnosis and scheduling of
these agents,
100,0000000 (109
)
99.999% or above = 999990000 cells
Remaining 0.001% = 100,0000000 –
999990000 = 10, 000

41. Approaches to Drug Treatment
• DARK BLUE LINE: Infrequent scheduling of treatment
courses with low (1 log kill) dosing and a late start prolongs
survival but does not cure the patient (i.e., kill rate <
growth rate)
• LIGHT BLUE LINE: More intensive and frequent
treatment, with adequate (2 log kill) dosing and an earlier
start is successful (i.e. kill rate > growth rate)
• GREEN LINE: Early surgical removal of the primary
tumour decreases the tumour burden. Chemotherapy will
remove persistent secondary tumours, and the total
duration of therapy does not have to be as long as when
chemotherapy alone is used.

42. Approaches to Drug Treatment –
Image from you Textbook

43. Resistance
Intrinsic and Acquired
Intrinsic: Some tumor types, e.g. malignant melanoma, renal cell cancer, and
brain cancer, exhibit primary resistance, i.e. absence of response on the first
exposure, to currently available standard agents
Acquired:
◦Single drug: change in the genetic apparatus of a given tumor cell with amplification or
increased expression of one or more specific genes
◦Multidrug resistance:
◦Resistance to a variety of drugs following exposure to a single variety of drug
◦increased expression of a normal gene (the MDR1 gene) for a cell surface glycoprotein (P-
glycoprotein) involved in drug efflux

44. Toxicity countering - common ones
Folinic acid rescue – Mtx (administration of > 100 fold dose of Mtx)
Systemic Mesna (sodium-2-mercaptoethane sulfonate) administration and irrigation by
acetylcysteine – detoxify toxic metabolites (cyclophosphamide)
Vomiting: Ondansetron
Amifostine (organic thiophosphate) - activation (cisplatin – nephrotoxicity))
Hyperurecaemia: uricosuric agents like allopurinol, alkalization of urine and plenty of fluid
Hypercalcaemia: Multiple myeloma, breast cancer etc. IV fluid and Bisphosphonates
Pulse therapy: 2 – 3 weeks intervals drug therapy
Platelet and granulocyte transfusion: to prevent bleeding and infection
Granulocyte colony stimulating factors (GM-CSF/G-CSF) – recovery of granulocytopenia
(myelosupression)

45. Thank you