Final results of a randomized phase III study evaluating the addition of oxaliplatin first line to 5-FU followed by irinotecan at progression in advanced colorectal cancer (LIFE study)

Abstract

3517 Background: The LIFE study was designed to demonstrate a 10% absolute improvement in survival at 2 years (from 20 to 30%), with the addition of oxaliplatin in first line to the 5-FU followed by irinotecan sequence in advanced colorectal cancer (ACRC). Method: A total of 725 ACRC patients from UK (46%), Poland (39%), other countries (15%), were randomized from March 2001 to March 2002 to receive 5-FU monotherapy (Lockich or de Gramont regimens) or the same regimen plus oxaliplatin 85mg/m2, repeated every 2 weeks. Second line therapy was standardized with irinotecan 350 mg/m2 single agent repeated every 3 weeks, in both arms. Results: Patients’characteristics were well balanced except for metastatic sites (liver + other in 88% versus 76% of patients receiving oxaliplatin/5FU or 5FU respectively). Safety results are in line with the safety profiles of the drugs, without any unexpected toxicities (Cassidy, ASCO 2003). Median number of cycles (10) was the same in both arms, with a higher dose of 5-FU in the control arm. Median cumulative dose of oxaliplatin was 845 mg/m2. Relative oxaliplatin dose intensity was 87%. Direct efficacy evaluation of the first line treatment showed improvement in response rate -RR- (54% versus 30%, p< 0.0001) and progression free survival -PFS- (7.9 versus 5.9 months, p <0.0001) in the oxaliplatin arm in accordance with previously reported trials. This did not translate into overall survival advantage (15.9 versus 15.2 months) with a median in the oxaliplatin arm below the 19–20 months obtained in more recent studies. Conclusion: These results confirm the improvement in RR and PFS observed with combination therapy in first line ACRC. Overall survival results could be explained by the low number of patients receiving second line irinotecan therapy in the oxaliplatin arm (41%) and thus exposed to the 3 active agents: 5-FU, oxaliplatin and irinotecan. No significant financial relationships to disclose.