Radiation Oncology/Colon/Randomized

Chemotherapy in Stage III

• CALGB 89803 -- 5-FU/LV vs. 5-FU/LV/IRI
  • Randomized. 1264 patients with completely resected Stage III colon CA. Treated with weekly bolus 5-FU/Leukovorin +/- irinotecan
  • 2007 PMID 17687149 -- "Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803." (Saltz LB, J Clin Oncol. 2007 Aug 10;25(23):3456-61.)
    • Outcome: No difference in DFS or OS
    • Toxicity: Significantly higher in 5-FU/LV/Irinotecan arm
    • Conclusion: Addition of irinotecan not beneficial in completely resected Stage III

Chemotherapy in Stage IV

• GONO Trial -- FOLFOXIRI vs. FOLFOX
  • Randomized. 244 patients, unresectable metastatic CRC, no prior chemo for advanced disease. Treated with 1) FOLFOXIRI (irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks) vs. FOLFIRI (infusional fluorouracil, leucovorin, and irinotecan). Primary end-point response rate (RR)
  • 2007 PMID 17470860 -- "Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest." (Falcone A, J Clin Oncol. 2007 May 1;25(13):1670-6.)
    • Toxicity: Grade 2-3 neurotoxicity 19% vs. 0% (SS), Grade 3-4 neutropenia (50% vs. 28%, SS)
    • Response rate: 66% vs. 41% (SS); better R0 secondary resection rate of mets
    • Outcome: median PFS 9.8 months vs. 6.9 months (SS); median OS 22.6 months vs. 16.7 months (SS)
  • Conclusion: FOLFOXIRI improves RR, PFS, and OS with manageable toxicity