Anal Cancer Treatment Protocols 

Updated: Apr 07, 2020
  • Author: Jeffrey B VanDeusen, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment Protocols

Anal cancer treatment protocols are provided below, including those for limited localized disease, metastatic disease, salvage therapy, and additional special considerations.

Limited localized disease

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]

  • 5-FU 1000 mg/m 2/day IV continuous infusion on days 1-4 and 29-32 (maximum daily dose of 5-FU of 2000 mg/day) plus  mitomycin 10 mg/m 2 IV bolus on days 1 and 29 (maximum 20 mg per dose)
  • 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]

  • Capecitabine 825 mg/m 2 PO BID, Monday–Friday, on each day that RT is given, throughout the duration of RT (typically 28 treatment days)  plus  mitomycin 10 mg/m 2 days 1 and 29 plus  concurrent RT  or
  • Capecitabine 825 mg/m 2 PO BID days 1–5 weekly x 6 weeks plus  mitomycin 12 mg/m 2 IV bolus day 1 plus concurrent RT

Metastatic disease

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:

  • Cisplatin 60 mg/m 2 day 1 plus  5-FU 1000 mg/m 2/d IV continuous infusion on days 1–4; repeat every 3 weeks  or
  • Cisplatin 75 mg/m 2 day 1  plus  5-FU 750 mg/m 2/d IV continuous infusion on days 1–4; repeat every 4 weeks 


  • Oxaliplatin 85 mg/m 2 IV day 1 plus
  • Leucovorin 400 mg/m 2 IV day 1 plus
  • 5-FU 400 mg/m 2 IV bolus on day 1, then 1200 mg/m 2/d x 2 days (total 2400 mg/m 2 over 46–48 hours) IV continuous infusion
  • Repeat every 2 weeks 

Carboplatin + paclitaxel

Subsequent therapy may include the following [2] :

Salvage therapy

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; the choice depends on patient performance status and degree of local failure.

Special considerations

See the list below:

  • Consider HIV testing and CD4 count analysis in patients with clinical risk factors.

  • No changes to therapy are indicated in HIV-infected 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/μL or if nadir platelet count is more than 50,000 but less than 85,000/μL, 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/μL, 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/μL or if the platelet count is less than 85,000/μL, delay chemotherapy 1wk [3]