A randomised phase II study comparing irinotecan (IRI) plus leucovorin (LV) and 5-fluorouracil (5FU) versus IRI-LV-5FU followed be oxaliplatin (OXA) plus LV-5FU in patients with previously untreated metastatic colorectal cancer (CRC)

3583 Background: IRI and OXA are both effective in the treatment of CRC. A theoretical framework supports the hypothesis that sequential administration of cytotoxic drugs at adequate doses can maximize the cell kill and overcome drug resistance. The aim of the study was to compare the response rate (RR), the time to tumor progression (TTP), the overall survival (OS) and to assess the toxicity profile of previously untreated patients with advanced CRC randomly assigned between IRI-LV-5FU (arm A) versus IRI-LV-5FU followed by OXA-LV-5FU (arm B). Methods: Intent to treat analysis was performed on 429 patients (219 in arm A and 210 in arm B) who were randomized from 31/10/2001 to 21/10/2004. The treatment schedules consisted of weekly IRI, 80 mg/m2 or OXA, 45 mg/m2 plus LV 200 mg/m2 followed immediately by intravenous bolus 5FU, 450 mg/m2 for 6 weeks followed by a 2-week rest period. Treatment was continued for 4 cycles, patients in arm B were treated initially with IRI-LV-5FU for 2 cycles followed by sequential administration of 2 cycles of OXA-LV-5FU. Results: The study failed to show any superiority of the sequential regimen. There were no significant differences between the two arms in the overall RR (26% versus 28%, p=0.631), TTP (Median, 7.8 versus 8.4 months, p=0.149). Toxicity profiles (grade III and IV) were equally frequent in both arms (diarrhea 13% versus 13.5%, febrile neutropenia 2% versus 1.5%, neurotoxicity 0% versus 0.5%). Conclusions: IRI-LV-5FU or IRI-LV-5FU followed by QXA-LV-5FU show equally substantial activities with manageable toxicity profile in advanced CRC. No significant financial relationships to disclose.