Randomized phase III trial comparing infused 5-fluorouracil/folinic acid (LV5FU) versus LV5FU+irinotecan (LV5FU+IRI) as adjuvant treatment after complete resection of liver metastases from colorectal cancer (LMCRC). (CPT-GMA-301)

Abstract

LBA4013 Background: 5FU regimens have been suggested to be effective in the adjuvant setting after LMCRC. Irinotecan (IRI) combined with infused 5FU regimens showed improvement in outcome of advanced colorectal cancer. The aim of this international, randomized trial was to compare the adjunction of IRI to FUFA in this setting. Methods: Main inclusion criteria: complete surgical resection (R0) of exclusively liver metastases with no prior treatment for metastatic disease. Patients were randomized to either: arm A, FA 400mg/m2/2h iv, 5FU 400mg/m2/2h bolus, followed by 2400 mg/m2/46h continuous infusion q2w for 12 cycles, or arm B, FUFA+IRI 180mg/m2/d1. The primary endpoint is disease-free survival (DFS). The analysis was planned after at least 147 events were observed and a minimum of 1 year of follow up in order to detect a hazard ratio of 0.64 (alpha=5%, power=85%). Secondary endpoints include safety and overall survival. Results: Between 12/2001 and 7/2006, 321 pts from 15 countries were randomized. The 2 arms were well balanced (Arms A/B): number treated 153/153, median age 61/63 years, male 65%/59%, and for the stratification factors, only 1 liver metastasis 64%/64%, prior adjuvant chemotherapy 35%/40%, and diagnosis of liver metastasis more than 1 year after resection of primary tumor 37%/39%. Median follow-up was 42 months for both groups. The overall HR for DFS adjusted for the stratification factors was 0.89 (95%CI: 0.66–1.19, log-rank p=0.47). Median DFS was 21.6 for FUFA vs 24.7 months for FOLFIRI. No significant treatment effect was observed for any level of the stratification factors. However, there was a tendency for improved DFS for patients treated with FOLFIRI within 42 days after surgery. Grade 3/4 toxicities (%) in Arms A/B were respectively: any toxicity 34/51, neutropenia 7/23, diarrhea 8/14, vomiting 3/5, nausea 3/3. Conclusions: These results indicate that there was no overall advantage in terms of DFS for the addition of IRI to FUFA. However, we cannot exclude a benefit for patients starting chemotherapy before 6 weeks after surgery. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer