A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer

Introduction

The aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC).

Materials and methods

191 chemotherapy-na?ve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3?months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint.

Results

183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3?% (p?=?0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2?months; p?=?0.475); progression-free survival (7.7 and 8.7?months; p?=?0.292), and response duration (6.4 and 7.6?months; p?=?0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p?p?=?0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p?=?ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6?weeks, and for body pain and emotional role functioning after 6 and 12?weeks; all of these favored the FOLFOX4 arm (p????0.05).

Conclusions

TOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens.