A phase III randomized trial of LV5FU2+CPT-11 vs. LV5FU2 alone in adjuvant high risk colon cancer (FNCLCC Accord02/FFCD9802)

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Abstract
3502 Background: LV5FU2+CPT-11 has shown more activity than LV5FU2 alone in first line metastatic colorectal cancer. This adjuvant trial evaluated the addition of CPT-11 to LV5FU2 in terms of Event-Free Survival (EFS) and safety in colorectal cancer patients (pts) at a high risk of relapse. Methods: Colon cancer pts with postoperative N2 or N1 detected by occlusion/perforation were randomized to either: A: LV5FU2 (leucovorin 200mg/m2 as a 2-h infusion, 5-FU 400mg/m2 bolus and 600mg/m2 22-h continuous infusion, d1–2) or B: LV5FU2+CPT-11 (irinotecan 180mg/m2 90-min infusion d1+LV5FU2) fortnightly for 12 cycles without any support of growth factors. Pts were stratified by center, type of detection, delay from surgery to chemotherapy (≤28d; >28d) and age (<65y;≥65y). A 0.64 hazard ratio was deduced from an expected change in 3-year EFS from 45% to 60% with 5% two-sided alpha and 85% power. ITT survival analysis used the Logrank test. Results: 400 pts were randomized 1:1 in 75 centers between 11/98 and 09/02. Median follow-up is 36 months. More T3/T4 (p<0.017), more 15+ positives nodes (p<0.014), more vascular invasion (p<0.031), and more perineural involvement (p80% for 95% and 77% in arms A and B (p80% for 70% pts. More NCI G3–4 neutropenia in arm B (4% vs. 28%pts, p<0.001) is related to the absence of G-CSF support. In spite of only 97% necessary events observed, there was no significant difference in EFS rates between the 2 treatment arms. Conclusions: The two arms were unbalanced for important prognostic factors. Adjuvant LV5FU2+CPT-11 as compared to LV5FU2 alone is associated with more G3–4 neutropenia. These preliminary results show no improvement between the 2 arms in terms of EFS in the ITT analysis. Final analysis will be presented with more follow-up. No significant financial relationships to disclose.

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