Trial Information

Phase 2 Trial to Assess the Efficacy and Safety of Chemoradiation With 5-fluorouracil, Mytomicin C and Panitumumab as a Treatment for Anal Squamous Cell Carcinoma

In the 1980s, the treatment of choice for anal cancer was abdominal-perineal amputation,
which included the removal of the anus, rectum and lymphatic drainage areas and a permanent
colostomy. With this treatment, 5-year survival rates were 40-70%. In the following years,
however, it was shown that anal cancer was a tumor that was sensitive to chemotherapy and
radiation, so surgery was not the first choice and was only reserved for resistant cases or
relapses. Concomitant chemo and radiotherapy based on the Mitomycin C - 5-FU regimen is
currently the standard treatment for localized (except T1N0) and locally advanced cases.
This statement is supported by two randomized studies that showed that the administration of
chemoradiation with Mitomycin C - 5FU was better than radiation in monotherapy. The trial
conducted by the United Kingdom Coordinating Committee on Cancer Research (UKCCCR)
randomized 585 patients to receive radiotherapy (45 Gy in 4-5 weeks) or the same
radiotherapy regimen coupled with 5-FU (1000 mg/m2 x 4 days or 750 mg/m2 x 5 days), for the
first and last week of radiotherapy and Mitomycin C 12 mg/m2 on day 1. The 3-year local
failure rate was 39% in the combined arm versus 61% with radiotherapy alone. There were no
differences in the 3-year overall survival rate. On the other hand, in the study conducted
by EORTC, 110 patients were distributed to receive radiotherapy (45 Gy in 5 weeks, with an
overimpression of 15 Gy in the patients with CR and 20 Gy if PR) or radiotherapy plus 5-FU
(750 mg/m2 days 1-5 and 29-33) associated to Mitomycin C (15 mg/m2 on day 1). The CR rate
was significantly greater in the group treated with chemoradiation (80% vs. 54%). After 5
years of follow-up, there was still an 18% increase in the local control rate in favor of
the group treated with chemoradiation.

More recently, the results of a phase II CALGB trial, suggests that the administration of
induction treatment with two cycles of cisplatin-5FU (cisplatin 100 mg/m2 on days 1 and 29
and 5FU 1000 mg/m2 days 1-4 and 29-32) followed by chemoradiotherapy with 5-FU and
Mitomycin C was very promising, especially in patients with a poor prognosis, with 50% of
patients remaining colostomy and disease-free at 48 months. However, in a randomized study
by the RTOG group, which included 682 patients, this strategy was compared with the classic
concomitant chemoradiation with 5-FU (1000 mg/m2 days 1-4 and 29-32) and Mitomycin C (10
mg/m2 days 1 and 29). No differences in survival were found, but it was also detected that
the colostomy rate was greater in the patients treated with the regimen containing Cisplatin
(HR, 1.68; 95% CI, 1.07-2.65; P=.02). The authors concluded that induction with cisplatin
was not superior to the traditional administration of 5FU-Mitomycin C with RT.

Epidermoid anal cancer is a tumor that often expresses the EGFR receptor. In an initial
study with 21 cases, it was reported that there was EGFR expression in all the biopsies. In
another study with 38 cases, it was found that 55% of the tumors expressed EGFR. No study
has been published, however, which has investigated the efficacy of Panitumumab in this
tumor. There is only one report of a refractory case in which cetuximab was administered
together with CPT-11 with an excellent response.