Journal of Clinical Oncology, Vol 21, Issue 7
(April), 2003: 1307-1312
© 2003 American Society for Clinical Oncology
Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
Werner Scheithauer,
Gabriela V. Kornek,
Markus Raderer,
Birgit Schüll,
Katharina Schmid,
Erwin Kovats,
Bruno Schneeweiss,
Fritz Lang,
Alfred Lenauer,
Dieter Depisch
From the Department of Internal Medicine I, Division of Clinical Oncology, University Hospital of Vienna, Vienna; Department of Internal Medicine, General Hospitals of Kirchdorf/Krems; and Departments of Surgery, General Hospitals of Baden, Neunkirchen, and Wiener Neustadt, Austria.
Address reprint requests to Werner Scheithauer, MD, Department of Internal Medicine I, Division of Clinical Oncology, University Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria; email: werner. scheithauer{at}akh-wien.ac.at.
Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study.
Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m2 day 1 plus capecitabine 2,000 mg/m2/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m2 days 1 and 14 combined with capecitabine 3,500 mg/m2 days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease.
Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%).
Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.
Supported, in part, by the Gesellschaft zur Erforschung der Biologie und Behandlung von Tumorkrankheiten.
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