Raltitrexed and mitomycin-C as third-line chemotherapy for colorectal cancer after combination regimens including 5-fluorouracil, irinotecan and oxaliplatin: A phase II study

Background: To investigate the therapeutic value and safety of a third-line treatment with raltitrexed and mitomycin-C (MMC) in patients with advanced colorectal cancer (ACC) pretreated with combination regimens including 5 fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP). Patients and Methods: A total of 21 patients (PS 112, 19/2; M/F 15/6; median age=73) with ACC, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, CPT-11 and L-OHP, were accrued in this study. At the time of their relapse, cytotoxic chemotherapy, consisting of intravenous raltitrexed 3mg/m(2) plus MMC 6mg/m(2) on therapeutic day 1, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease, unacceptable toxicity or, patient refusal occurred. Results: All the patients were assessable for toxicity and 16 for response evaluation, having completed at least two courses of chemotherapy. The overall response rate was 0%. Seven patients (33.3%) had a stable disease and nine patients (43%) progressed. The median time to progression was 2.3 months (95% CI: 1.65-2.95%) and median overall survival (OS) 5 months (95% CI: 2.52-7.48%). No toxic deaths occurred. Third-line treatment tolerance was generally mild to moderate and easy to treat. WHO grade 314 anemia, neutro- and thrombocytopenia occurred in 9.5%, 4.7% and 4.7% of the patients, respectively. However, these toxicities did not have a significant impact on global quality of life. Conclusion: Our data suggest that the association of raltitrexed and MMC in patients with ACC pretreated with combination regimens including 5-FU, CPT-11 and L-OHP is feasible and could contribute to increase patients' OS time. Further evaluation of this regimen seems to be warranted.