OPTIMOX 1 study : FOLFOX 7/LV5FU2 compared to FOLFOX 4 in patients with advanced colorectal cancer. A de Gramont, A Cervantes, T André, A Figer, G Lledo, M Flesch, G Russ, E Quinaux, E Carola, PL Etienne. GERCOR, Paris, France.
Background: FOLFOX4 has shown superiority over LV5FU2 in first line therapy of advanced colorectal cancer. FOLFOX7 combines a simplified (s) LV5FU2 regimen and high-dose oxaliplatin. The limiting toxicity of the FOLFOX4 regimen is a cumulative sensory neurotoxicity which imposes to stop therapy in patients still responding to therapy.
Methods: OPTIMOX study is a phase III trial comparing in first line therapy FOLFOX4 until progression (arm A) to FOLFOX7 x 6 cycles followed by simplified LV5FU2 x 12 cycles and FOLFOX7 reintroduction (arm B). 526 patients = 75 years and with Alk Ph < 3-time the UNL were enrolled. Patients characteristics (%) are in arm A, 262 pts : M/F= 58/42, PS 0/1-2= 55/45, median age= 63 yrs(29-75) ; in arm B 264 pts : M/F= 62/38 , PS 0/1-2= 56/44, median age= 63yrs (32-75).
Results: Grade 3-4 toxicity (% of pts) was in arm A/B : neutrophils 31.7/21.5, platelets 2.7/10.3, nausea 5.8/10.0, mucositis 2.7/6.1, diarrhea 10.8/12.3, HFS 0.4/3.5, neurotoxicity 18.2/13.0. Response rate (ITT) was 58.5% in arm A and 58.3% in arm B. In arm A and B, median PFS were respectively 9.2 and 9.0 months (n.s.), median OS were respectively 20.0 and 21.6 months (n.s.). The primary endpoint of this study is the time of disease control (TDC). Median TDC was 9.2 months in arm A and 9.7 in arm B (n.s.). Oxaliplatin was reintroduced in 40% of the patients in arm B; responses were observed in 10.4% of the patients and stabilisation in 32.0% (ITT). 27 patients had oxaliplatin reintroduction in arm A and 52 received oxaliplatin-based therapy in subsequent lines. Overall 23.8% of patients in arm A and 48.7% in arm B received at least two oxaliplatin-based therapy. Not reintroducing oxaliplatin was protocol violation in 21% of the patients in arm B. In a multivariate analysis, prognostic factors were performance status, number of metastatic sites, LDH, alk phosphatases and oxaliplatin reintroduction.
Conclusion: FOLFOX7 followed by sLV5FU2 has a similar toxicity and efficacy than FOLFOX4 but is more convenient. There was a large variation among centers on oxaliplatin reintroduction which appears as a major prognostic factor. These results allow us to start a new investigational study OPTIMOX2 comparing this OPTIMOX 1 strategy versus FOLFOX7x 6 cycles followed by a treatment break and reintroduction of FOLFOX7.