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Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study

Charles S. Fuchs, John Marshall, Edith Mitchell, Rafal Wierzbicki, Vinod Ganju, Mark Jeffery, Joseph Schulz, Donald Richards, Raoudha Soufi-Mahjoubi, Benjamin Wang, José Barrueco

From the Dana-Farber Cancer Institute, Boston, MA; Georgetown University Lombardi Cancer Center, Washington, DC; Jefferson Medical College, Philadelphia, PA; US Oncology Network, Virginia Oncology Associates, Newport News, VA; US Oncology Network, Tyler Cancer Center, Tyler, TX; Pfizer Global Pharmaceuticals, New York, NY; Lakeridge Health Oshawa, Oshawa, Ontario, Canada; Frankston Hospital, Frankston, Australia; and Christchurch Hospital, Christchurch, New Zealand

Address reprint requests to Charles S. Fuchs, MD, Dana-Farber Cancer Institute, 44 Binney St, Office Dana 1232, Boston, MA 02115; e-mail: charles_fuchs{at}dfci.harvard.edu

Purpose This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).

Patients and Methods A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.

Results Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of grade 3 hypertension than mIFL+Bev.

Conclusion FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.

Supported by Pfizer Inc, New York, NY.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006 Atlanta, GA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Updated Results From the BICC-C Study
  Charles S. Fuchs, John Marshall, and José Barrueco
  JCO 2008 26: 689-690 [Full Text]
• Capecitabine and Irinotecan As First-Line Treatment of Advanced Colorectal Cancer
  Cornelis J.A. Punt and Miriam Koopman
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