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

Cristina Gravalos, Antonieta Salut, Carlos García-Girón, Rocío García-Carbonero, Ana Isabel León, Isabel Sevilla, Joan Maurel, Beatriz Esteban, Eduardo García-Rico, Adolfo Murias, Hernán Cortés-Funes, Cristina Gravalos, Antonieta Salut, Carlos García-Girón, Rocío García-Carbonero, Ana Isabel León, Isabel Sevilla, Joan Maurel, Beatriz Esteban, Eduardo García-Rico, Adolfo Murias, Hernán Cortés-Funes

Abstract

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-naïve 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 < 0.0001) and leukopenia (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.

Figures

Fig. 1
Fig. 1
Disposition of patients
Fig. 2
Fig. 2
Kaplan–Meier estimates of overall survival
Fig. 3
Fig. 3
Kaplan–Meier estimates of time to disease progression

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