Purpose: The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV).
Methods: Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47-70), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days.
Results: Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2-8.5), and median overall survival (OS) 8 months (range, 4.0-12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1-2: 52%-grade 3: 28%, and anemia grade 1-2 only: 36%. Mild mucositis grade 1-2 occurred in 13.5% of patients and was the principal non-hematologic toxicity.
Conclusion: Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.