Are two too many when it comes to the treatment of anal canal cancer with concurrent radiation and mitomycin C?

Abstract

3 Background: Concurrent chemoradiation (CRT) with 2 doses of 5-fluorouracil (5-FU) and mitomycin C (MMC) is the standard of care for anal canal cancer (ACC) in North America while 1 dose of MMC is an acceptable practice. Given the lack of randomized data of 1 vs 2 doses of MMC on disease outcomes, we have conducted a population-based study to elucidate the impact of 1 vs. 2 doses of MMC on patterns of treatment failure (POF) and outcomes in ACC treatment. Zainab Al Habsi, Aswin Abraham, Mustafa Al Balushi, Gabriella Tankel, Karen Mulder, Heather Warkentin, Dan Schiller, Keith Tankel, Nawaid Usmani, Diane Severin, Kim Paulson, Hatim Karachiwala, Clarence Wong, Tirath Nijjar, Kurian Joseph. Methods: Data was collected from the provincial cancer registry of patients with stage I-III ACC who were treated with concurrent CRT from 2000 to 2018. Recurrence free survival (RFS), overall survival (OS), and ACC specific survival were calculated. Results: 428 patients with a median age of 58 years (29-88 years) were included in this analysis. 234 (54.7%) patients received 1 dose of MMC and 194 (45.3%) received 2 doses of MMC. At a median follow-up of 78.5 months (5-252 months), 89 (20.8%) patients developed disease recurrence: 44 (10.3%) loco-regionally, 39 (9.1%) distally and 6 (1.4%) had both local and distant recurrences. Cox Regression analysis showed that the dosage of MMC did not have an impact on overall recurrence (HR = 0.883, p = 0.561), whereas stage III was associated with increased risk for recurrence (HR = 5.238, p = 0.021). Subgroup analysis showed an association of stage IIIb and IIIc with recurrence (HR = 13.33, p = 0.008 and HR = 6.933, p = 0.011 respectively), but was not impacted by the use of 1 vs. 2 doses of MMC. The dosage of MMC did not show any association with local recurrence (HR = 1.136, p = 0.655) or distant recurrence (HR = 0.743, p = 0.267). However, in Stage IIIc patients, 2 doses of MMC showed a trend towards improved distant RFS (HR = 0.626,p = 0.084). Conclusions: Our analysis showed that the patterns of failure and the risk of loco-regional and distant failures were similar between patients who received 1 vs. 2 doses of MMC for stage groups I to IIIc. These finding support routine use of single dose of MMC along with 5FU and radiotherapy for definite chemoradiation. However, a trend towards better RFS was demonstrated with a second dose of MMC in patients with stage IIIc disease.