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Reintroduction of Oxaliplatin Is Associated With Improved Survival in Advanced Colorectal Cancer

Aimery de Gramont, Marc Buyse, Jose Cortinas Abrahantes, Tomasz Burzykowski, Emmanuel Quinaux, Andres Cervantes, Arie Figer, Gérard Lledo, Michel Flesch, Laurent Mineur, Elisabeth Carola, Pierre-Luc Etienne, Fernando Rivera, Isabel Chirivella, Nathalie Perez-Staub, Christophe Louvet, Thierry André, Isabelle Tabah-Fisch, Christophe Tournigand

From the Hôpital Saint Antoine; Hôpital Tenon; Sanofi-aventis, Paris; Clinique Saint Jean, Lyon; Hôpital Devron, Dijon; Clinique Sainte Catherine, Avignon; Hôpital de Senlis, Senlis; and Clinique Radiologique Armoricaine, Saint Brieuc, France; International Drug Development Institute, Louvain-la-Neuve; Hasselt University, Hasselt, Belgium; Hospital Clínico Universitario, Valencia; Hospital Universitario Marques de Valdecilla, Santander, Spain; and Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel

Address reprint requests to Aimery de Gramont, MD, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France; e-mail: aimery.de-gramont{at}sat.aphp.fr

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.

Supported by the Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR), Paris, France.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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				D. Sargent and A. Grothey Sound Footing or Slippery Slope? The Value of Secondary Analyses of Randomized Trials J. Clin. Oncol., August 1, 2007; 25(22): 3191 - 3193. [Full Text] [PDF]