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

mFOLFOX:

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

Carboplatin area under the curve (AUC) 5 (see Carboplatin AUC Dose Calculation [Calvert formula]) IV day 1 plus
Paclitaxel 175 mg/m ² IV day 1
Repeat every 21 days

Subsequent therapy may include the following^[2]:

Nivolumab 240 mg or 3 mg/kg every 2 wk or
Pembrolizumab 200 mg or 2 mg/kg every 3 wk

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]