PDF Format

1. Colorectal Cancer and
Targeted Therapy
Ann Marie Siney, RN, ANP‐BC
N214 Spring 2012

2. Colorectal Cancer
 3rd most common cancer in US
 3rd cause of cancer death in US
 2012 estimated new cases; 103,170 Colon and
40,290 Rectal
 Incidence & Death Rate decreasing over last 20yrs
 Over 90% of cases occur > age 50
 Incidence is rising in < 50 age group

3. Colorectal Cancer
 Sex: incidence equal men/women until age 50;
then becomes higher in men than women
 Incidence and mortality greater in men than
women – 35% to 40% overall
 Race/ethnicity: incidence & deaths highest in
blacks, lowest in Indian/Alaska Natives &
Hispanics

4. Risk Factors
 Age: peak incidence 6th/7th decades
 Personal and/or family history of CRC
 Adenomatous colonic polyps >2 mm
 Inflammatory Bowel Disease
 Ulcerative colitis & Crohn’s disease
 Genetic mutations; 5‐6% of all CRC’s
 FAP (Familial polyposis) 100% risk
 HNPCC (Hereditary nonpolyposis colorectal cancer)
 Type 2 DM

5. Risk Factors
Modifiable
 Obesity
 Sedentary lifestyle
 Smoking
 Heavy Alcohol Use
 Dietary
 ↑ in red, processed meat
 ↓ in fruits and vegetables

6. Decreased Risk
 Low fat, high fiber diet
 Exercise
 Vitamins D, calcium,
 Estrogen replacement therapy (HRT) post‐
menopausal, NSAIDs
 Colectomy for high risk FAP

7. Screening Tests
 Goal: detect & remove adenomatous polyps
 Begin age 50
 Increased surveillance for those at high risk
 1st degree relative begin 10yrs prior to dx
 Hx of polyps, genetic mutations etc.
 Collaborative effort – ACS, ACR, US CRC task
force.

8. CRC Screening at Age 50

9. Fecal Occult Blood Test
 2/3 of colon cancers and some polyps bleed
 Avoid foods for 3 days before exam that can alter test
results:
 Aspirin
 NSAIDs, such as ibuprofen (Advil, Motrin, others)
 Anticoagulants, such as warfarin (Coumadin)
 Artichokes, fresh broccoli, cabbage, cauliflower,
cucumbers, horseradish, mushrooms, potatoes,
radishes and turnips
 Meat and fish
 Vitamin C supplements
 Iron supplements

11. Colonscopy
 Similar equipment and patient
positioning for sigmoidoscopy
 Underutilized
 Sedation recommended
 Full bowel prep required
 If heart valve disease – must have
antibiotics before and after
 Arrange for transportation
will be dizzy (due to meds)
after procedure

12. Computer Tomographic
Colonography
 Virtual Colonscopy – CTC

13. Carcinogenesis
 Malignant Transformation
 Metaplasia
 Dysplasia
 Carcinoma in situ
 Invasive cancer
 Metastasis

18. Carcinogenesis
 Key genes mutated
 Oncogenes
 Tumor suppressor genes
 DNA repair genes
 Signaling cascade
 Tumor micro environment

21. Targeted Therapies
 Monoclonal Antibody Mab
 Large molecules ‐ IV
 Extracellular targets
 Prevent ligand binding
 Stimulate the immune system
 Tyrosine kinase inhibitors
 Small molecules ‐ Oral
 Multiple Targets ‐ outside and inside the cell
 Inhibit signaling cascade

22. Signs and Symptoms
 Right Sided
 Vague, dull pain, dark stools, mass RLQ
 Anemia – fatigue, wt loss, weakness
 Left Sided
 ↑gas, pain, cramps, bright red blood,
 Change in bowel habit – const/diarr
 ∆ in caliber of stool – Obstruction
 Rectal – fullness, frank blood, tenesmus

23. Pathophysiology
Colon vs Rectal Cancer
 Adenocarcinoma; >90%, arising in glandular
epithelial tissue of mucosa
 Squamous cell; < 10%
 Metastasis
 lymphatic, venous,
 direct extension, implantation
 1° Liver, Lungs, Peritoneal Cavity
 also bone, adrenals, ovary, brain
 Colon → liver Rectal → lung

24. Colorectal Case Study
 52 yr old African American male
 Last physical 5yr ago
 H&P: occasional blood on stool denies
pain, ∆ in bowel habit, wt loss or fatigue
 Family; Dad died 50ish, unknown

25. CRC Case Study
 Physical Exam WNL
 Non distended, +BS x 4, ‐ pain, HSM or masses, DRE
neg
 Differential Dx
 Tests : CBC (anemia)
 Refer to GI for colonoscopy
 Invasive adenoca of sigmoid colon

26. Diagnostic Studies
 Staging work up
 CBC, CMP, CEA, +/‐ CA19‐9, bili
 CT scan of chest, abdomen & pelvis to r/o
metastatic disease
 PET scan
 Surgical Consult
 Medical Oncology Consult

27. Surgical Op>ons
 Colon cancer, Goal: Cure
 Hemicolectomy
 Laparoscopic vs laperotomy
 Colostomy: rare, d/t bowel obstructed temporary vs
permanent
 Resection of Liver or Lung Metastasis
 Intent to cure
 May include RFA (radiofrequency ablation)
 May need neo‐adjuvent chemo to downstage

28. Surgical Op>ons
 Rectal Cancer , Goal: Cure
 Prevent local recurrence
 Maintain bowel, bladder and sexual function
 Maintain & improve pts QOL
 20% impotency, sexual dys, urinary retention, bladder
dys, fecal incont & urgency, stoma

29. Surgical Op>ons
 Rectal Cancer
 TAE: small early stage lesions, 8cm from anal verge
 TME: resects node bearing mesorectum, ↓ local recurrence
from 30% to <10%
 Low ant resection: proximal lesions, >6cm from anal verge
 AP resection: <6cm from anal verge, colostomy

30. Colorectal Case Study
 Surgical consult
 CT CAP w & w/out contrast
 CMP, CEA, PT, PTT, EKG, CXR
 L hemicolectomy w/anastomosis
 6cm moderately differentiated invasive
adenocarcinoma
 Pathology pending

31. Staging Criteria
 Pathologic/histologic stage
 T: depth of tumor penetration into &
through the intestinal wall
 N: regional lymph node involvement
 M: absence or presence of distant
metastases
 G: Grading 1‐4, degree of differentiation
 AJCC 7th Edition

33. Pathologic Review
 TNM classification with Grade
 Margins – proximal, distal, radial
 K Ras mutation gene analysis
 Wild‐type vs mutation at codon 12 &13
 Mutations occur in 30‐50% CRC
 Indicate resistance to anti – EGFR mabs
 MSI‐H vs MSI‐L, BRAF, p53

34. TNM Stages for CRC
STAGE T N M
I T1 or T2 NO MO
IIA T3 NO MO
IIB T4a NO MO
IIC T4b NO MO
IIIA T1‐T2 N1 MO
T1 N2a MO
IIIB T3‐T4a N1 MO
T2‐T3 N2a MO
T1‐T2 N2b MO
IIIC T4a N2a MO
T3‐T4a N2b MO
T4b N1‐N2 MO

35. TNM STAGES FOR CRC
STAGE T N M
IVA Any T Any N M1a
Any T Any N M1b

36. Chemotherapy
A Brief History
 5FU/LV – 50 yrs ago, ↑ OS ‐ 12m
 CPT‐11 – late 90’s IFL, FOLFIRI
 Oxaliplatin – FOLFOX4
 ↑ OS from 10‐12mths to 14‐16mths
 N9741 Trial – best combination
 FOLFOX – response rate, ↑OS 19.5m, s/e profile,
 FDA approved 2004 for mCRC

37. Chemotherapy & Targeted Therapy
 Oral 5FU equivalent to IV 5FU
 Xelox equivalent to FOLFOX
 FOLFOX ≈ FOLFIRI in mCRC
 Targeted Therapies
 Bevacizumab (Avastin)
 Cetuximab (Erbitux)
 Panitumumab (Vectibix)
 With chemo ↑OS to >20mths

39. Angiogenesis
 VEGF: Vascular Endothelial Growth Factor

41. EGFR Inhibitors

43. Treatment, Colon Ca
 Stage I Colon Cancer
 Surgical Resection & Observation
 Surveillence x 5 years
 H&P, CEA, CT CAP +/‐ PET scan
 Colonoscopy

44. Stage II Colon Ca
 Surgical Resection & dilemma
 Observation vs Adjuvent Therapy x 6m
 ↓ Risk – Obs vs 5FU vs clinical trial
 ↑ Risk – Obs vs FOLFOX vs clinical trial
 High Risk Features
 T4 lesion, perforation, + margins, < 12 LN,
 MSI‐L stability, lymphovascular invasion, Grade 3‐4,

45. Stage III Colon Ca
 Surgical Resection & Adjuvent Chemotherapy x 6mths
 FOLFOX q2w x 12 cycles
 Folinic Acid, 5FU, Oxaliplatin
 Restaging – CEA, CT CAP, +/‐ PET,
 Colonoscopy w/in 1 yr of surgery
 Surveillence x 5 years

46. Stage IV Colon Ca
 Single Met in Liver or Lung
 Surg: resect colon and met lesion
 Adj chemo: Avastin + Folfox x 6mth
 Restage and surveillance
 Multiple Mets
 Adj chemo: Avastin + Folfox or other
 Restage in 2mths for surg resection and efficacy of
chemotherapy

47. Rectal Cancer
 Stage I ‐ resection & observation
 Stage II, Stage III, early Stage IV
 neo‐adj chemo/rad: cont 5FU/rad x 6wk, Oxaliplatin now
being used
 followed by surgical resection
 Followed by adjuvent chemo x 4 mths FOLFOX
 Avastin w resected Stage IV

48. Rectal Caner
 Stage IV – widely metastatic
 Combination chemo + Avastin may be given to control
disease prior to starting chemo/radiation
 Avastin is not given during XRT

49. NP Role
 H&P
 Assess physical and mental health
 Assess pts knowledge of dz and dx
 Staging
 Path review for staging
 Review CT/PET, labs: CEA, CBC, CMP, LFT’s

50. NP Role
 Treatment Planning
 Baseline labs/scans, +/‐ port‐a‐cath
 Educate: tx, schedule, side effects
 Write chemo orders, prescriptions
 Tx plan to billing/authorization
 Management
 Tolerance, side effects, response
 Complications

51. CRC Case Study
 Surg: left hemicolectomy & port
 Path: T3, N1, +2/14LN Mx, G2, KRAS wild‐type gene
 CT CAP scan negative
 Pre‐op CEA 56, kidney, liver wnl
 Treatment plan ?

52. Treatment Plan
 Labs: CBC, CMP, CEA
 PET scan ‐ baseline
 FOLFOX6 q2wks x 12 cycles
 Education
 Schedule of tx, chemo s/e, pump
 Who and when to call
 Rx for anti‐nausea

53. Side Effects
 IV 5FU & Oral Xeloda
 Mucositis
 Nausea, vomiting
 Diarrhea
 Palmar‐Plantar Erythrodysesthesia
 Neutropenia

54. Irinotecan, FOLFIRI
 Nausea, vomiting: mild – severe
 Utilize combination anti‐emetics
 Diarrhea – dose limiting s/e
 Loperamide q2h until resolved
 Myelosuppression –dose limiting
 Parameters to hold or dose reduce
 Alopecia ‐ complete
 Fatigue ‐ moderate

55. Oxalipla>n, FOLFOX
 Nausea, vomiting, fatique: mild‐mod
 Myelosuppression
 Thrombocytopenia: does adjust
 Neuropathy
 Transient numbness tingling 1‐5d
 Hands, feet, oral, exacerbated by cold
 *Cumulative dose dependant & limiting
 Persists between cycles, stocking/glove, hold/reintroduce when
resolved

56. Avas>n, Bevacizumab
 HTN (RPLS)
 Monitor q visit, QD, tx with anti‐HTN
 Reversable Proteinuria
 Monitor urine ea tx, hold for 3+,
 Hypothyroidism
 TSH at baseline & q2mth, Synthroid

57. Avas>n
Black Box Warning
 Hemorrhage –
 Epistaxis – fatal hemorrhagic events
 Wound Healing Complications
 Hold therapy pre & post surgery
 GI Perforations
 abdo pain, constipation, vomiting

58. Erbitux & Vec>bix
 Infusion reaction: Loading dose
 Premedicate with anti‐histamine
 Administer over 2hrs, then 60m,
 Stop Drug, fluids, benadryl, steroid
 Acne like rash
 Grade 1‐4, onset w/in 2wks of tx
 Lotions, oral antibiotics, steroids
 Diarrhea: 25% mild

59. Erbitux rash
 Face, neck, chest and back
 Grade I ‐ macular papular rash
 Grade II – pruritis +/‐ interfering
with daily life
 Grade III – severe erythroderma,
vesicular eruptions
 Grade IV – ulcerating, blistering,
exfoliative dermatitis
Image: ONS SIG newsletter, April 2005

60. EGFR Inhibitors
 Hypomagnesia
 Cause: renal wasting
 ↑ likelihood with ongoing tx, 50%
 Monitor Mg q mth
 Replace orally at least 400mgs QD
 IV replacement

61. NP role in Management
 Tolerance to therapy
 Management of side effects
 Adjustment to chemo regimen
 Coping with dz and therapy
 Supportive therapy/Advocate for pt
 Advanced disease
 Restaging PET/CT
 Monitor markers

62. Colorectal Case Study
 S/P FOLFOX x 6 cyles
 Mild nausea x 2d,
 Neuropathy: fingertips to nailbed, resolves
w/in 10d
 Plts 75k
 PE – WNL
 Plan ?

63. CRC Case Study
 Tolerating tx well overall
 Nausea – discuss interventions
 Thrombocytopenia ‐ Dose adjustments, discuss signs
and symptoms
 Neuropathy – discuss symptoms & continue to
monitor

64. Complica>ons
 Side Effects to Tx
 Bowel Obstruction
 DVT
 Biliary Obstruction
 Ascites
 Pain

65. Recurrent Disease
 Progressive Disease
 Advanced Disease
 Treat vs stop therapy
 Hospice
 End of Life Issues

66. Reference List
 ACS (2012), Colorectal Facts & Figures 2011
 ACS (2008), Colorectal Facts & Figures 2008‐2010.
 Davies, L. & Goldberg, R., (2008). First‐Line Therapeutic Strategies in
Metastatic Colorectal Cancer. Oncology.
 Dotan, E., Browner, I., Hurria, A & Denlinger, C. (2012) Challenges in
the Management of Older Patients with Cancer.
 Lindsetmo, R.O., Yong & Delaney, (2009), Surgical treatment for
Rectal Cancer: An International Perspective
 Meyerhardt, J. & Mayer, R. (2009). Drug Therapy; Systemic Therapy
for Colorectal Cancer. NEJM.

67. Reference List
 Morse, M. (2006), Supportive Care in the Management of Colon
Cancer, Supportive Cancer Therapy
 NCCN (2012), Clinical Practice Guidelines in Oncology, Colorectal
Cancer.
 http://www.cancer.gov/flash/targetedtherapies/flex/main.
html
 http://www.cancerstaging.org/staging/posters/colon8.5x11.
pdf