One Compared with Two Cycles of Mitomycin C in Chemoradiotherapy for Anal Cancer: Analysis of Outcomes and Toxicity

Abstract

(1) Background: Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation. However, administration of the second bolus of mmc has been based largely on centre preference. Given limited published data on outcomes with different mmc regimens, our objective was to compare the efficacy and toxicity of 1 compared with 2 cycles of mmc in acc treatment. (2) Methods: Our retrospective study evaluated 169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free (dfs) and overall survival (os) were analyzed. (3) Results: Baseline demographics, performance status, and stage were similar in the groups of patients who received mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were comparable, except for white blood cell count, which was higher in the mmc2 group, but within normal range. The 5-year os and dfs were similar (75.1% and 54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively). On multivariate analysis, mmc2 was the factor most strongly associated with specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01), grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001). (4) Conclusions: In definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes similar to those achieved with 2 cycles, with significantly less acute toxicity.

PET-CT guided SIB-IMRT combined with concurrent 5-FU/MMC for the treatment of anal cancer

“…A recently published retrospective study found no difference in 5-year DFS or OS between patients receiving one or two doses of MMC. On multivariate analysis, two cycles of MMC was the factor most strongly associated with grade 3þ skin toxicity (hazard ratio: 4.76; p < .001) and grade 3þ leukopenia (hazard ratio: 4.82; p < .01), which were reported in 72.8% and 45.7% of cases (73% and 43% in our series) [27]. It remains so far unclear whether the second dose of MMC improves efficacy, or merely increases toxicity.…”

Systematic review of outcome measures following chemoradiotherapy for the treatment of anal cancer (CORMAC)

“…Where disease‐free survival was reported, the outcome was defined in 20 studies, using nine different definitions (Table ). The most commonly used definition (local, regional or distant failure, second primary or death from any cause) was used in five studies . Four of these studies are from the same research organization (Radiation Therapy and Oncology Group) including two papers reporting short‐ and long‐term results of the same study .…”

Intensity-Modulated Radiotherapy (IMRT) vs Helical Tomotherapy (HT) in Concurrent Chemoradiotherapy (CRT) for Patients with Anal Canal Carcinoma (ACC): an analysis of dose distribution and toxicities

“…Three-year OS, DFS and CFS Kaplan Meier estimates were also similar. A recent retrospective study by our group suggests reduction of grade 3+ hematological and skin toxicities with 1 MMC cycle versus 2 cycles in ACC treatment, without compromise to OS, CFS and DFS [ 24 ]. Potential differences in acute toxicities secondary to different chemotherapy regimens may have been mitigated by radiotherapy technique.…”