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Rectal Cancer Medication

  • Author: Burt Cagir, MD, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
 
Updated: Mar 11, 2016
 

Medication Summary

The goals of pharmacotherapy are to down-stage the tumor, induce remission, reduce morbidity, and prevent complications.

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Antineoplastic agents

Class Summary

The recommendations from National Comprehensive Cancer Network 13th Annual Conference are outlined as follows. The use of as many chemotherapy drugs as possible is recommended to maximize the effect of adjuvant therapies for colon and rectal cancer. Bevacizumab in combination with chemotherapy is indicated in patients with positive or negative resectable synchronous metastases. For colon and rectal cancer, bevacizumab in combination with chemotherapy is also indicated in patients with unresectable synchronous metastases. FOLFOX —a combination of folinic acid, fluorouracil, and oxaliplatin — is reasonable to use for high-risk or intermediate-risk stage II patients (see Table 5).

FOLFOX is not indicated for good-risk or average-risk stage II patients. In patients in whom 5-fluorouracil treatment has failed, capecitabine should be avoided. Patients who experience no benefit from bevacizumab regimens should avoid continuing the therapy. Cetuximab should not be replaced with panitumumab. Patients with KRAS mutations should not be treated with cetuximab or panitumumab, as these mutations confer resistance to epidermal growth factor receptor (EGFR) inhibitors.

Fluorouracil (5-FU, Fluorouracil, Adrucil)

 

Blocks methylation of deoxyuridylic acid to thymidylic acid, thereby interfering with DNA synthesis. Dose is body-weight dependent and varies with specific protocol in which patient is involved.

Vincristine (Vincasar PFS, Oncovin)

 

Mechanism of action uncertain. May involve decrease in reticuloendothelial cell function or increase in platelet production. It is mitotic spindle inhibitor.

Leucovorin (Wellcovorin)

 

Potentiates effects of fluorouracil. Reduced form of folic acid that does not require enzymatic reduction reaction for activation. Allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis.

Given just prior to fluorouracil.

Irinotecan (Camptosar, Camptothecin-11, CPT-11)

 

Inhibits topoisomerase I, inhibiting DNA replication and, consequently, cell proliferation.

Oxaliplatin (Eloxatin)

 

A platinum-based antineoplastic agent used in combination with an infusion of 5-fluorouracil (5-FU) and leucovorin for the treatment of metastatic colorectal cancer in patients with recurrence or progression following initial treatment with irinotecan, 5-FU, and leucovorin. It forms interstrand and intrastrand Pt-DNA crosslinks that inhibit DNA replication and transcription. The cytotoxicity is cell-cycle nonspecific.

Cetuximab (Erbitux)

 

Recombinant human/mouse chimeric monoclonal antibody that specifically binds to the extracellular domain of human epidermal growth factor receptors (EGFR, HER1, c-ErbB-1). Cetuximab-bound EGF receptor inhibits activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased production of matrix metalloproteinase and vascular endothelial growth factor. Indicated for treating irinotecan-refractory, EGFR-expressed, metastatic colorectal carcinoma. Treatment is preferably combined with irinotecan. May be administered as monotherapy if irinotecan is not tolerated.

Bevacizumab (Avastin)

 

Indicated as a first-line treatment for metastatic colorectal cancer. Murine-derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). Inhibiting new blood vessel formation denies blood, oxygen, and other nutrients needed for tumor growth. Used in combination with standard chemotherapy.

Panitumumab (Vectibix)

 

Recombinant human IgG2 kappa monoclonal antibody that binds to human epidermal growth factor receptor (EGFR). Indicated to treat colorectal cancer that has metastasized following standard chemotherapy.

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Vaccine

Class Summary

HPV is associated with about 90% of anal cancer. In a study of homosexual males, HPV vaccine was shown to be 78% effective in prevention of HPV 16- and 18-related anal intraepithelial neoplasms. A study by Nielsen et al examined trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark from 1978-2008 and found that HPV vaccines may be a vital factor in the prevention of anal cancer and its precursor lesions.[64]

Papillomavirus vaccine, quadrivalent (Gardasil)

 

Quadrivalent human papillomavirus (HPV) recombinant vaccine. Vaccine efficacy mediated by humoral immune responses following immunization series. Indicated for prevention of anal cancer and associated precancerous lesions caused by HPV types 6, 11, 16, and 18 people aged 9-26 years.

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Contributor Information and Disclosures
Author

Burt Cagir, MD, FACS Clinical Professor of Surgery, The Commonwealth Medical College; Attending Surgeon, Assistant Program Director, Robert Packer Hospital; Attending Surgeon, Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Coauthor(s)

Douglas R Trostle, MD, MBA, FACS Chairman of Surgery, The Guthrie Clinic

Douglas R Trostle, MD, MBA, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, American Association for Physician Leadership, American College of Surgeons, Pennsylvania Medical Society, Society for Surgery of the Alimentary Tract, American Association of Endocrine Surgeons, American Society of General Surgeons, American College of Surgeons Oncology Group

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center

N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society

Disclosure: Nothing to disclose.

Additional Contributors

Philip Schulman, MD Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center

Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Acknowledgements

Elizabeth Cirincione, MD Director of Colon and Rectal Surgery, Department of Surgery, Nassau University Medical Center

Disclosure: Nothing to disclose.

Wendy Hu, MD Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center

Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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Diagnostics. Staging and workup of rectal cancer patients.
Staging and treatment. Rectal cancer treatment algorithm (surgery followed by adjuvant chemotherapy and radiotherapy). Initial stages are Endorectal ultrasound staging (uT).
Table 1. Comparison of AJCC Definition of TNM Staging System to Dukes Classification.
Rectal Cancer Stages TNM Staging Duke Staging 5-Year Survival
Stage I T1-2 N0 M0 A >90%
Stage II A T3 N0 M0 B 60%-85%
B T4 N0 M0 60%-85%
Stage III A T1-2 N1 M0 C 55%-60%
B T3-4 N1 M0 35%-42%
C T1-4 N2 M0 25%-27%
Stage IV T1-4 N0-2 M1 5%-7%
Table 2. Acceptable Minimal Distal and Proximal Resectional Margins for Rectal Cancer. [26]
Resection Margins Proximal Resection Margin(cm) Distal Resection Margin (cm)
Ideal Margins 5 cm or more 2 cm or more
Minimally acceptable margins 5 cm or more 1 cm or more
Table 3. Colorectal Chemotherapeutic Regimens
COLON AND RECTAL CANCER



COMMON CHEMOTHERAPY REGIMENS



FOLFOX (every 2 weeks) Oxaliplatin 85 mg/m2 day 1



Leucovorin 200 mg/m2 day 1



5-FU 400 mg/m2 IV Bolus day 1 and 2



5-FU 600 mg/m2 IV Infusion day 1 and 2 (22 hours)



FOLFOX 4



(every 2 weeks)



(4 cycles)



Oxaliplatin 85 mg/m2 day 1



Leucovorin 200 mg/m2 day 1



5-FU 400 mg/m2 IV Bolus day 1 and 2



5-FU 2400 mg/m2 IV Infusion day 1 (46 hours)



mFOLFOX 6



(Every 2 weeks)



(4 cycles)



Oxaliplatin 85 mg/m2 day 1



Leucovorin 400 mg/m2 day 1



5-FU 400 mg/m2 IV Bolus day 1 and 2



5-FU 1200 mg/m2 IV Infusion day 2 days



CapeOX



(Twice daily x 14 days)



(every 3 weeks)



Oxaliplatin 130 mg/m2 day 1



Capecitabine 850 mg/m2 PO BID for 14 days



FOLFIRI



(every 2 weeks)



Irinotecan 165 mg/m2 day 1



Leucovorin 200 mg/m2 day 1



5-FU 400 mg/m2 IV Bolus day 1 and 2



5-FU 600 mg/m2 IV Infusion day 1 and 2 (22 hours)



FOLFOXIRI



(every 2 weeks)



Irinotecan 180 mg/m2 day 1



Oxaliplatin 85 mg/m2 day 1



Leucovorin 200 mg/m2 day 1



5-FU 3200 mg/m2 IV Infusion day (48 hours)



Bevacizumab 5-10 mg/kg IV every 2 weeks with chemotherapy
Cetuximab 400 mg/m2 IV day 1, then 250 mg/m2 IV weekly
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