Effectiveness and tolerability of FOLFOXIRI regimen in the third- and subsequent lines of therapy in patients with metastatic colorectal cancer.

Abstract

e15584 Background: Options of therapy are limited for patients with colorectal cancer who developed disease progression during standard 5-FU-, oxaliplatin-, and irinotecan-contained regimens. There is straight information about synergy of irinotecan (SN-38) and oxaliplatin gained from fundamental and early clinical trials. We aimed to analyze effectiveness and safety of triple drug-combination of 5-FU, oxaliplatin and irinotecan (FOLFOXIRI) in heavily pretreated patients with metastatic colorectal cancer. Methods: Patients with a metastatic colorectal cancer who received more than 2 lines of standard 5-FU-, oxaliplatin- and irinotecan-based doublet regimens with or without targeted therapy were included. Reinduction of chemotherapy in previous lines was allowed. The retrospective analysis of medical histories was done. Eligible patients had to receive number of cycles that were sufficient for response rate estimation. Disease response was evaluated according to RECIST 1.1 criteria. Survival analysis was performed using the Kaplan-Meier method. Tolerability was estimated by CTCAE v. 5.0. Results: Forty-six patients were included in retrospective per protocol analysis. The median follow-up was 19 months. The median number of previous lines of chemotherapy was 2 (2-6). Primary resistance to oxaliplatin- and irinotecan-based chemo during previous lines was noted in 20 patients (43%) and 16 patients (35%), respectively, while seven patients (15%) developed the primary resistance to both agents given in a sequential order. All patients were treated with targeted therapy during previous treatment lines. The median of FOLFOXIRI cycles was 8 (range, 2-19). Two patients (4%) were treated with FOLFOXIRI without any targeted agents. The objective response rate was 33% (n = 15). The disease stabilization was reached in 43% (n = 20). The disease control rate was 76% (n = 35). Eleven patients (24%) had the progression of disease at the first follow-up. The median progression free survival and median overall survival were 6 months and 11 months, respectively. Toxicity was evaluated in 35 patients. The most common severe adverse events (grade 3 and 4) were neutropenia (46%) and fatigue (26%). Treatment was delayed in 20 patients (57%), and 13 patients (37%) required dose reduction. One patient had to discontinue treatment due to unacceptable toxicity. Conclusions: According to our study FOLFOXIRI provides the objective response and increased life expectancy in heavily pretreated patients. The further assessment of FOLFOXIRI regimen for refractory colorectal cancer in the prospective trials is needed.