Reviewer: Dr Scott Berry Date posted: June 21, 2007 OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC). A GERCOR study. Reviewer: Dr Scott Berry Date posted: June 21, 2007

Rationale The OPTIMOX1 trial randomized patients with metastatic colon cancer who had received 3 months of FOLFOX induction therapy to continued FOLFOX vs q 2 weekly infusional 5FULV maintenance with re-introduction of FOLFOX when tumours had progressed beyond their baseline size

Rationale The OPTIMOX 1 trial demonstrated that the FULV maintenance strategy generally reduced toxicities but did not reduce survival (Tournigand JCO 2006) OPTIMOX 2 was designed to see whether the 5FULV maintenance could be omitted in favour of a “chemotherapy free interval” after FOLFOX induction

Rationale The OPTIMOX 1 trial introduced the concept of Duration of Disease Control: J Clin Oncol 24:394-400, 2006 by American Society of Clinical Oncology

R OPTIMOX 1: mFOLFOX7 x 6 cy 5FULV maintenance until progression Primary Outcome: OS OPTIMOX 1: mFOLFOX7 x 6 cy 5FULV maintenance until progression Then FOLFOX7 reintroduction R OPTIMOX 2: mFOLFOX7 x 6 cy No maintenance until progression Then FOLFOX7 reintroduction Untreated Metastatic Colon Cancer

Interval (median, weeks) RESULTS Optimox 1 Optimox 2 p-value Chemo Free Interval (median, weeks) N/A 17 DDC (median, weeks) 52 39 P=0.39 OS (median, mos) 26 19 P=0.0549

STUDY COMMENTARY The OPTIMOX2 strategy of 3 month induction chemo followed by a chemo free interval results in a clinically significant (borderline statistical significance) detriment in overall survival Why? ? Longer induction ? Shorter break before re-introduction Labianca - ASCO 2006 Intermittent FOLFIRI 2 mos on / 2 mos off vs Continuous FOLFIRI demonstrated equivalent survival ? Different maintenance strategy DREAM (OPTIMOX3) - Bevacizumab/Erlotonib vs Bevacizumab maintenance after FOLFOX+Bev induction

BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS The current variable availability of oxaliplatin as first line therapy for metastatic colon cancer likely limits the use of an “OPTIMOX” strategy For Canadian oncologists contemplating an induction maintenance strategy after 3 months of FOLFOX chemotherapy, the 5FULV component of therapy should be continued as maintenance therapy after induction Other intermittent chemotherapy strategies such as that reported by Labianca at ASCO 2006 have decreased exposure to chemo without a detriment in survival