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Reviewer: Dr Christopher Booth Date posted: June 21, 2007

Peri-operative FOLFOX4 chemotherapy and surgery for resectable liver metastases from colorectal cancer Plenary Session ASCO 2007 Authors: B. Nordlinger on behalf of EORTC Intergroup Study 40983. Reviewer: Dr Christopher Booth Date posted: June 21, 2007. Treatment A:

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Reviewer: Dr Christopher Booth Date posted: June 21, 2007

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  1. Peri-operative FOLFOX4 chemotherapy and surgery for resectable liver metastases from colorectal cancerPlenary Session ASCO 2007Authors: B. Nordlinger on behalf of EORTC Intergroup Study 40983 Reviewer: Dr Christopher Booth Date posted: June 21, 2007

  2. Treatment A: Pre-op: 6 cycles of FOLFOX 4 Surgery Post-op: 6 cycles of FOLFOX 4 R Treatment B: Surgery alone • Potentially resectable liver • mets of CRC origin • Up to 4 lesions on CT scan • No other sites of disease • No prior oxaliplatin • ECOG 0-2

  3. RESULTS

  4. STUDY COMMENTARY • Pre-op FOLFOX 4 was well tolerated and delivered with >90% dose intensity. One patient did not go to surgery due to chemo-related liver toxicity. • In pre-op group there was progressive disease in 6.6% of patients (n=12). 4/12 patients were resected. • 83% of patients in both arms were resected. • Increased rate of post-operative complications in group that received chemotherapy (25 vs 16%, p=0.04). Post-operative mortality no different (1 pt in chemo arm, 2 pts in surgery alone arm). • 37% of patients in chemo arm did not receive post-operative FOLFOX.

  5. BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS • This well designed RCT evaluated a question which is commonly encountered in clinical practice for which there have previously been minimal data available (and none with combination chemo). • Despite the trade-off in post-operative complications, there was a clinically meaningful improvement in PFS. • ? Will this translate into a an impact in overall survival • Comparable benefits seen with 5FU/FA (7% DFS benefit at 5 yrs, Portier et al, JCO 2006) • Other questions which remain unanswered include the optimum timing of peri-operative chemotherapy (peri-op vs post-op alone) and the optimal use of modern systemic agents.

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