Anal Cancer 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 and mitomycin, as well as radiotherapy. There is some controversy regarding substituting cisplatin for mitomycin in limited-stage disease (conflicting clinical trial results), so the National Comprehensive Cancer Network (NCCN) solely recommends the following:

Mitomycin + 5-FU + radiotherapy ^{[2, 3]} {ref3] 10 :

• 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

Metastatic disease

Stage IV (any T, any N, M1):

Metastatic disease is commonly treated with cisplatin-based chemotherapy. The recommended therapy includes the use of 5-FU and cisplatin chemotherapy.

Cisplatin + 5-FU ^[4] :

• 5-FU 1000 mg/m ²/day IV continuous infusion on days 1-5 plus  cisplatin 100 mg/m ² IV on day 2; repeat every 28d until disease progression
• Capecitabine has been assessed as a replacement for 5-FU in a phase II trial, but there is insufficient evidence to recommend substitution to date ^[5]
• Systemic therapy for metastatic anal cancer is limited; published reports are few for cisplatin/5-FU; one study of 19 patients noted a 66% response rate, with a median survival of 34.1mo in a highly selected patient population ^[4]
• Other systemic therapy regimens have been published, but only in limited-stage studies, and their use is not currently recommended

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 and 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 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 ^[6]
• 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/m ² from 10 mg/m ²
• 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/m ² from 10 mg/m ²
• 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]