Use of Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer (MCRC): A Post-Hoc Analysis of the Glutox Study

Abstract

Introduction: Oxaliplatin-based chemotherapy has significantly improved overall survival in first-line therapy for patients having CRC, either in adjuvant or metastatic settings. The objective of this post-hoc analysis conducted in mCRC patients of the GLUTOX study (Samson et al. Eur J Cancer 2013, 49(S2): S518) is to provide Canadian-based data on treatment patterns and efficacy. Methods: The GLUTOX study was a Canadian, multicenter, randomized, open-label, phase III clinical trial with CRC patients treated in first-line with an oxaliplatin-based chemotherapy regimen either in adjuvant or metastatic settings. Adult oxaliplatin-naïve patients with ECOG ≤2 were included and patients were excluded if they were previously or currently diagnosed with a peripheral sensory neuropathy. Of the 200 patients enrolled in GLUTOX, 58 had mCRC. Efficacy, quality of life and safety data were analysed in the subgroup of mCRC patients. Results: Patients with mCRC had a median age of 58 years (range of 33 to 75) and were mostly men (62.1%) and whites (96.6%). Primary tumor site was colon in 77.6% of patients. Patients were ECOG 0 (77.6%) and 1 (22.4%). Median duration of disease was 1.5 months (range 0.1 to 156.7). The oxaliplatin-based chemotherapy regimens were mFOLFOX6 (87.9%), FOLFOX4 (8.6%) and XELOX (3.4%) with 60.3% of patients receiving bevacizumab. Adverse events (35.1%) were the main reason for withdrawal from the study. A median of 10 cycles (range of 1 to 12) of oxaliplatin was received. 43.1% of patients had progressed during the study and the median progression-free survival was 638 days. 60.3%, 53.4% and 41.4% of patients reached respectively 8, 10 and 12 cycles of oxaliplatin-based chemotherapy regimen. Mean/median number of cycles received were 8.2/10 cycles. The overall/oxaliplatin median relative dose intensities (%) at cycles 8, 10 and 12 were respectively 100/100, 96/94 and 98/94. The overall response rate was 68.9%. On the FACT/GOG NTX-12 where a higher score indicates better QoL, a median increase of 3 points (range -6 to 29) from baseline to end of treatment was observed. At the 3 months follow-up visit, 48.2% of patients were receiving a chemotherapy regimen: FOLFOX (37.0%), 5FU/leucovorin (29.6%) and FOLFIRI (11.1%). 53.4% of patients reported grade 3/4 toxicities up to 30 days after the last oxaliplatin dose and the most frequent were neutropenia (29.3%), diarrhea (6.9%), peripheral neuropathy (6.9%) and febrile neutropenia (5.2%). Conclusion: Oxaliplatin-based chemotherapy remains the most frequent choice worldwide in first-line for patients with CRC. Canadian mCRC patients had a higher response rate and a lower rate of grade 3/4 neutropenia, diarrhea and sensory toxicities compared to de Gramont et al. (J Clin Oncol 2000, 18:2938-2947). The Canadian mCRC patients analyzed in this post-hoc analysis had a 5 year younger median age and a better ECOG profile (0% vs 10% ECOG 2) than those studied by de Gramont et al. This Canadian multicenter post-hoc analysis is important as it provides insights of treatment patterns and progression-free survival.