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Multicenter Phase II Study of Nordic Fluorouracil and Folinic Acid Bolus Schedule Combined With Oxaliplatin As First-Line Treatment of Metastatic Colorectal Cancer

From the Department of Oncology and Section of Oncology, Institute of Medicine, Haukeland University Hospital, Bergen; Department of Oncology, Ullevål University Hospital; The Norwegian Radium Hospital, Oslo; Division of Hematology and Oncology, Rogaland Central Hospital, Stavanger, Norway; Departments of Oncology, Radiology, and Clinical Immunology, Uppsala University Hospital, Uppsala; and Radiumhemmet, Karolinska Hospital, Stockholm, Sweden

Address reprint requests to H. Sørbye, MD, PhD, Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway; e-mail: half{at}helse-bergen.no

PURPOSE: This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer.

PATIENTS AND METHODS: Eighty-five patients were treated with oxaliplatin 85 mg/m² as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m² and, 30 minutes later, by a bolus injection with FA 60 mg/m² every second week. The same doses of FU and FA were also given on day 2.

RESULTS: Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients).

CONCLUSION: Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.

Supported by The Norwegian Cancer Society, The Swedish Cancer Society, and Sanofi Winthrop.

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

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