Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer. A meta-analysis of two randomized trials

Abstract

3524 Background: Adjuvant systemic chemotherapy (CT) administered after resection of colorectal cancer (CRC) metastases (M) may reduce the risk of recurrence and improved survival but its benefit has never been demonstrated. Two phase III trials (FFCD 9002 and EORTC/NCIC CTG/GIVIO (ENG) trials) with a very similar design showed a trend for improvement in survival after adjuvant CT but had to close prematurely because of slow accrual, lacking the statistical power to demonstrate any significant difference in survival. We report here a pooled analysis based on individual data from these trials. Methods: Patients were required to have a WHO performance status ≤2 and a histologically proven CRC with a complete (R0) surgical resection of the primary tumour and of ≤4 liver or lung metastases. They were randomized between chemotherapy (CT arm) [5FU 400 mg/m2 (FFCD) or 370 mg/m2 (ENG) IV q.d. x 5 days plus dl-leucovorin 200 mg/m2 (FFCD) or l-leucovorin 100 mg/m2 (ENG) IV q.d. x 5 days, 6 cycles at 28 days intervals] or surgery alone (S arm). Results: 129 pts were included in the ENG trial between 1994 and 1998, 173 in the FFCD trial between 1991 and 2001. 24 pts (ENG: 22, FFCD: 2) were excluded from analysis for missing post-baseline data: 278 pts were included in the present analysis (CT: 138, S: 140). Patients’ characteristics by treatment arm (% CT/S): males 58.0/63.6, age <70 years: 79.7/79.3, stage IV primary tumor: 29.0/47.1 (p=0.02), liver M 94.2/93.6, ≥2 M resected: 33.3/31.4. Conclusion: Adjuvant CT with a 5FU bolus based regimen tends to improve survival after complete resection of CRC metastases. The observed improvement in median PFS was almost statistically significant whereas the improvement in median OS (more than 1 year) was not (lack of statistical power?). This pooled analysis supports the use of adjuvant CT, with a more effective regimen, after potentially curative resection of CRC metastases. Updated results will be presented. (Supported by AROLD) [Table: see text] No significant financial relationships to disclose.