Sequential compared to combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (ACC): A Dutch Colorectal Cancer Group (DCCG) phase III study

4012 Background: Overall survival (OS) in phase III studies with 1st line combination therapy in ACC may be influenced by imbalances in salvage treatments. This is the first study that prospectively investigates the sequential vs the combined use of all available effective cytotoxic drugs. Methods: Previously untreated patients (pts), WHO PS 0–2 were randomized between 1st line capecitabine (Cap), 2nd line irinotecan (Iri), and 3rd line Cap + oxaliplatin (CapOx) (Arm A, sequential) vs 1st line CapIri and 2nd line CapOx (Arm B, combination). The dose of Cap was 1250 mg/m2 (mono) or 1,000 mg/m2 (combination) b.i.d. day 1–14, Iri 350 mg/m2 (mono) or 250 mg/m2 (combination), and Ox 130 mg/m2. All cycles were q 3 weeks with Iri/Ox given i.v. on day 1. Response was assessed q 3 cycles. Primary endpoint was OS. The study was designed to detect a 20% reduction in the hazard of death (HR=0.80) for an increase in median OS from 14 to 17.5 months (a=0.05, 2-tailed test). Results: 820 pts were randomized between Jan ...