P-324 - Mitomycin-c (mtc) as salvage therapy for patients with metastatic colorectal cancer (mCRC)

Abstract

Introduction: For patients with mCRC and disease progression after the available standard cytotoxic and biologic agents, treatment options outside the context of a clinical trial are limited. Mitomycin-C is an old cytotoxic drug that has been used for a variety of solid tumor types in the past. It is still used in some instances for treatment of patients with mCRC in good performance status as salvage therapy. Methods: At the IORS, we retrospectively reviewed patients with mCRC who were treated with mitomycin-C as salvage therapy in a five-year period. All patients had previously received at least two chemotherapy regimens with or without biological agents. Data concerning demographic characteristics, previous treatment, number of cycles of mitomycin-C, toxicity and treatment outcome were analysed. Results: In the period between January 2011 and December 2016, 46 patients were treated with mitomycin-C as salvage therapy, 26 male (56.5%) and 20 female (43.5%), with median age at diagnosis 57 years, range 34 to 73. All patients had previously received oxaliplatin and irinotecan based chemotherapy, with 8 patients (17.4%) also having received bevacizumab in the first line, while 12 patients (21.4%) had treatment with cetuximab in the third line as per reimbursement availability in Serbia (K-ras wild type tumours). Mitomycin-C was administered at a dose of 8 mg/m2 every three weeks as monotherapy (10 pts, 21.7%) or in combination with fluoropyrimidines: capecitabine 1000 mg twice daily (2000 mg per day) days 1 to 14 every three weeks (11 pts, 23.9%), or infusional 5FU per DeGramont regimen (25 pts, 54.4%). ECOG performance status (PS) of our patients at the start of mitomycin-C therapy was: PS0 13 pts (28%), PS1 32 pts (70%) and PS2 1 patient (2%). Dominant metastatic sites were: liver in 35 patients, lung in 9, peritoneum in 9, ovary in 6, while 14 patients had more than one metastatic site. Median number of cycles of mitomycin-C was 4, range 1 to 12. Best response to mitomycin-C therapy was partial response in 1 patient (2%), stable disease in 15 patients (33%), and progression in 30 patients (65%). Two patients were still on mitomycin-C treatment at the cut-off time. Median progression-free survival (mPFS) during mitomycin-C treatment was 2.6 months (2.2-3.1m, CI 95%). There were no statistically significant differences in mPFS between men and women, ECOG performance status at start of MTC therapy, patients with primary left versus right colon tumors, nor depending on localisation of metastatic site(s). Median overall survival in this group of patients was 43 months (35.9-50.1m, CI 95%). Nine patients are still alive at the time of this analysis. Ten patients experienced grade 3 haematologic toxicity, all of them receiving the combination MTC-DeGramont therapy, but were able to complete treatment. There were no grade 4 toxicities. Conclusion: In this study mitomycin-C+/-fluoropyrimidines showed a modest efficacy and a favourable toxicity profile as salvage regimen in mCRC, in a population of patients with prolonged survival. It may be considered for patients with mCRC in good PS who received all available therapies and are not eligible for clinical studies.