Reintroduction of Oxaliplatin Is Associated With Improved Survival in Advanced Colorectal Cancer
Authors:
- Aimery de GramontAGAimery de Gramont
- Marc BuyseMBMarc Buyse
- Jose Cortinas AbrahantesJAJose Cortinas Abrahantes
- Tomasz BurzykowskiTBTomasz Burzykowski
- Emmanuel QuinauxEQEmmanuel Quinaux
- Andres CervantesACAndres Cervantes
- Arie FigerAFArie Figer
- Gérard LledoGLGérard Lledo
- Michel FleschMFMichel Flesch
- Laurent MineurLMLaurent Mineur
- Elisabeth CarolaECElisabeth Carola
- Pierre-Luc EtiennePEPierre-Luc Etienne
- 1 August 2007
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 25 (22) , 3224-3229
Abstract
Purpose: In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups. Patients and Methods: A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin reintroduction in the center. An adjusted hazard ratio (HR) was calculated for three reintroduction classes (1% to 20%, 21% to 40%, and > 40%), using centers with no reintroduction (0%) as the reference group. Results: Oxaliplatin reintroduction had an independent and significant impact on OS (HR = 0.56, P = .009). The percentage of patients with oxaliplatin reintroductions also had a significant impact on OS. Centers in which more than 40% of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced. Conclusion: Oxaliplatin reintroduction is associated with improved survival in patients with advanced colorectal cancer.Keywords
This publication has 20 references indexed in Scilit:
- OPTIMOX1: A Randomized Study of FOLFOX4 or FOLFOX7 With Oxaliplatin in a Stop-and-Go Fashion in Advanced Colorectal Cancer—A GERCOR StudyJournal of Clinical Oncology, 2006
- Oxaliplatin reintroduction in patients previously treated with leucovorin, fluorouracil and oxaliplatin for metastatic colorectal cancerAnnals of Oncology, 2004
- Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal CancerNew England Journal of Medicine, 2004
- Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal CancerNew England Journal of Medicine, 2004
- A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal CancerJournal of Clinical Oncology, 2004
- Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal CancerNew England Journal of Medicine, 2000
- Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal CancerJournal of Clinical Oncology, 2000
- Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trialThe Lancet, 2000
- Partial residuals for the proportional hazards regression modelBiometrika, 1982
- Regression Models and Life-TablesJournal of the Royal Statistical Society Series B: Statistical Methodology, 1972