Annals of Oncology 13:558-565, 2002
© 2002 European Society for Medical Oncology
Capecitabine (Xeloda®) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors
1Department of Oncology, Hospital Clínico Universitario San Carlos, Madrid, Spain; 2CRC Department of Medical Oncology, Beatson Oncology Centre, Western Infirmary, Glasgow, UK; 3Medical Oncology Service, Hospital Vall d’Hebron, Barcelona, Spain; 4Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK; 5Productos Roche SA, Madrid, Spain
Received 13 June 2001; revised 18 September 2001; accepted 25 September 2001.
Objectives
This phase I, dose-escalation study was conducted to determine the recommended dose of intermittent oral capecitabine in combination with a fixed dose of i.v. oxaliplatin. Secondary objectives included evaluation of the safety profile and antitumor activity.
Patients and methods
Twenty-three patients with advanced or metastatic solid tumors received a 21-day regimen of oral capecitabine (500, 825, 1000 or 1250 mg/m2 twice daily, days 1–14) in com-bination with oxaliplatin (130 mg/m2, 2-h i.v. infusion, day 1). Dose-limiting toxicities were determined during the first treatment cycle, and safety and efficacy were evaluated throughout treatment.
Results
The recommended dosing schedule is oral capecitabine 1000 mg/m2 twice daily (days 1–14) with i.v. oxaliplatin 130 mg/m2 (day 1) in a 21-day treatment cycle. The principal dose-limiting toxicity was diarrhea. The most frequent treatment-related adverse events occurring during the study were gastrointestinal (nausea/vomiting, diarrhea) and neurological (dysesthesia, paresthesia). The majority of treatment-related adverse events were mild to moderate in intensity, and no grade 4 adverse events occurred in the 15 patients treated at or below the recommended dose. The most common grade 3/4 laboratory abnormalities were lymphocytopenia (52% of patients), thrombocytopenia (22%; grade 3 only), neutropenia (17%) and hyperbilirubinemia (17%). Among patients treated at or below the recommended dose level (n = 15), only two patients experienced grade 3 neutropenia and no patients experienced grade 4 neutropenia. Partial tumor responses occurred in six patients (26%), including five of nine patients (55%) with colorectal cancer. All responding patients were pretreated with 5-fluorouracil and four responders had received prior irinotecan.
Conclusions
Oral capecitabine with i.v. oxaliplatin is a feasible combination regimen that shows promising antitumor activity in patients with colorectal cancer. There is an ongoing, phase II study to further characterize the safety and efficacy of this combination as first-line therapy for metastatic colorectal cancer, using the recommended dose identified in this study.
Key words: capecitabine, colorectal cancer, fluoropyrimidine, oxaliplatin
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