Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials.

PURPOSE Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. PATIENTS AND METHODS After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). RESULTS A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. CONCLUSION This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.

[1]  W. Enker,et al.  Liver resection for colorectal metastases. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  T. Hickish,et al.  Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. , 2004, The New England journal of medicine.

[3]  M. Makuuchi,et al.  Control arm for surgery alone is needed but difficult to obtain in randomized trials for adjuvant chemotherapy after liver resection for colorectal metastases. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  L H Blumgart,et al.  Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. , 1999, The New England journal of medicine.

[5]  S. Alberts Evolving role of chemotherapy in resected liver metastases. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  S. Lipsitz,et al.  Abstracts reprinted from Journal of Clinical Oncology , 2002, Annals of Surgical Oncology.

[7]  Thomas Gruenberger,et al.  Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial , 2008, The Lancet.

[8]  T. Grube,et al.  [Resection of colorectal liver metastases. What prognostic factors determine patient selection?]. , 2001, Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen.

[9]  M. Gonen,et al.  Hepatic arterial infusion after liver resection. , 2005, The New England journal of medicine.

[10]  B. Nordlinger,et al.  Surgical resection of colorectal carcinoma metastases to the liver: A prognostic scoring system to improve case selection, based on 1568 patients , 1996, Cancer.

[11]  L H Blumgart,et al.  Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. , 1999, Annals of surgery.

[12]  J. Bosset,et al.  Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.