Objectives: Capecitabine (CAP) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of their combination in patients with refractory solid tumors.
Patients and methods: Thirty-three pretreated patients with histologically confirmed inoperable neoplasms were enrolled. The patients' median age was 64 years, 21 were males, and 27 had a WHO performance status of 0-1. OX was administered on days 1 and 8, as a 3-hour intravenous infusion, at escalated doses ranging from 50 to 70 mg/m(2). CAP was administered orally for 14 consecutive days, at escalated doses ranging from 1,200 to 2,100 mg/m(2)/day. Treatment was repeated every 3 weeks.
Results: At the dose of 2,100 mg/m(2) (Xeloda) and 70 mg/m(2) (OX), all 3 enrolled patients presented DLT (grade 3 diarrhea, grade 3 asthenia and grade 3 neurotoxicity, respectively), and, thus, the recommended MTD for future phase II studies are 2,000 mg/m(2) for CAP and 70 mg/m(2 )for OX. A total of 145 treatment cycles were administered. Toxicity was very mild. Grade 2/3 neutropenia was observed in 4 (3%) treatment cycles. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (7 cycles; 5%), grade 2/3 neurotoxicity (10 cycles; 7%), grade 2/3 asthenia (8 cycles; 5.5%) and grade 2/3 diarrhea (6 cycles; 4%). There was no treatment-related death. One (4%) complete remission, 2 (8%) partial remissions, and 9 (36%) cases of stable disease were observed among 25 evaluable patients.
Conclusions: The results demonstrate that CAP and OX can be safely combined at clinically relevant doses and that this regimen merits further evaluation.
Copyright 2004 S. Karger AG, Basel