Anal Cancer Treatment Protocols
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Anal cancer treatment protocols are provided below, including those for limited localized disease, metastatic disease, salvage therapy, and additional special considerations.
Stage I-III (any T, any N, M0):
Current primary recommendations for non-metastatic anal cancer include concurrent chemotherapy and radiation therapy. [1] Common drugs include 5-fluorouracil (5-FU) and mitomycin; capecitabine may be substituted for 5-FU. There is some controversy regarding substituting cisplatin for mitomycin in limited-stage disease (conflicting clinical trial results); the National Comprehensive Cancer Network (NCCN) lists 5FU plus cisplatin and radiation therapy as a category 2B rcommendation. [2]
Mitomycin + 5-FU + radiotherapy [2, 3]
Radiotherapy (RT) should be included with all stages of disease; minimum of 45 Gy given over 5wk
Additional RT of 9-14 Gy may be considered for patients with T3, T4, or node-positive disease or in those with residual disease after an initial 45 Gy
Mitomycin + capecitabine + RT [2]
Stage IV (any T, any N, M1):
Metastatic disease is commonly treated with platinum-based chemotherapy. Regimens may include 5-FU or other agents. [2, 4]
Cisplatin + 5-FU:
mFOLFOX:
Carboplatin + paclitaxel
Subsequent therapy may include the following [2] :
See the list below:
Salvage therapy may be needed for recurrent or persistent disease after the use of chemoradiotherapy
Local recurrences may be successfully salvaged with surgery; however, locally recurrent anal squamous cell carcinoma poses a greater problem and higher rate of morbidity
In a 1999 analysis of 185 patients who received either radiotherapy or chemoradiotherapy between 1976 and 1996, a total of 42 went on to develop local failure; 26 of these patients had salvage therapy consisting of abdominoperineal resection, and of these patients, 43% had long-term 5-y survival and control of their disease [4]
Additionally, in the trial by Flam et al, 25 patients with positive post-treatment biopsies went on to receive salvage chemotherapy with cisplatin and 5-FU; 22 had subsequent biopsies, and 12 (55%) of the post-treatment biopsies in this setting were negative; 4 of 12 remained disease free at 4y; [3] either cisplatin or 5-FU is an acceptable option and depends on patient-performance status and degree of local failure
See the list below:
Consider HIV testing and CD4 count analysis in patients with clinical risk factors
No changes to therapy in HIV patients; however, consider dose reduction of mitomycin in patients with low CD4 counts and a history of complications such as opportunistic infections or other malignancies [5]
Mitomycin + 5-FU: If nadir WBC count is less than 2400 but more than 1000 or if nadir platelet count is more than 50,000 but less than 85,000, the second dose of mitomycin is reduced to 7.5 mg/m2 from 10 mg/m2
If nadir WBC count is less than 1000 or if platelet count is less than 50,000, the second dose of mitomycin is reduced to 5 mg/m2 from 10 mg/m2
If on day 28 the WBC count is less than 2400 or if the platelet count is less than 85,000, chemotherapy is delayed 1wk [3]
Matalon SA, Mamon HJ, Fuchs CS, Doyle LA, Tirumani SH, Ramaiya NH, et al. Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy. Radiographics. 2015 Nov-Dec. 35 (7):2090-107. [Medline].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. Available at http://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. Version 1.2018 — February 6, 2018; Accessed: April 30, 2018.
Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996 Sep. 14(9):2527-39. [Medline].
Eng C, Chang GJ, You YN, Das P, Rodriguez-Bigas M, Xing Y, et al. The role of systemic chemotherapy and multidisciplinary management in improving the overall survival of patients with metastatic squamous cell carcinoma of the anal canal. Oncotarget. 2014 Nov 30. 5 (22):11133-42. [Medline]. [Full Text].
Bilimoria KY, Bentrem DJ, Rock CE, et al. Outcomes and prognostic factors for squamous-cell carcinoma of the anal canal: analysis of patients from the National Cancer Data Base. Dis Colon Rectum. 2009 Apr. 52(4):624-31. [Medline].
Cummings BJ, Keane TJ, O’Sullivan B, Wong CS, Catton CN. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys. 1991 Oct. 21(5):1115-25. [Medline].
White EC, Goldman K, Aleshin A, Lien WW, Rao AR. Chemoradiotherapy for squamous cell carcinoma of the anal canal: Comparison of one versus two cycles mitomycin-C. Radiother Oncol. 2015 Sep 4. [Medline].
Jeffrey B VanDeusen, MD, PhD Fellow, Department of Hematology/Oncology, Duke University School of Medicine
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee
Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
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.
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