A dose escalation study of docetaxel plus capecitabine in combination with oxaliplatin in patients with advanced solid tumors.

OBJECTIVES: Capecitabine (CAP), Oxaliplatin (OX) and Docetaxel (DOC) have shown considerable 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 toxicities (DLTs) of their combination in patients with advanced solid tumors.

PATIENTS AND METHODS: Twenty-one patients were enrolled. The patient's median age was 68 years, 15 were male, and 12 were chemo-naïve. DOC was administered on day 1 as an 1-hour (iv) infusion at a standard dose of 50 mg/m(2). OX was administered on day 1 as a 2-hour (iv) infusion at escalating doses ranging from 70-80 mg/m(2). CAP was administered orally on days 1 to 7 at escalating doses ranging from 2,000-2,750 mg/m(2) given as two daily divided doses. Treatment was repeated every two weeks.

RESULTS: Six different dose-levels were examined. At dose-level VI, two of three enrolled patients presented DLTs (one patient diarrhea and asthenia grade 3 and another grade 3 diarrhea), and thus, the recommended MTD for future phase II studies is CAP 2,750 mg/m(2) , DOC 50 mg/m(2) and OX 75 mg/m(2). A total of 121 treatment cycles were administered. Grade 3 neutropenia was observed in six (5%) treatment cycles and grade 3 thrombocytopenia in one (1%). There was no febrile episode. Grade 3 asthenia was observed in three (14%) patients, grade 3 diarrhea in four (19%), grade 3 neuropathy in one (5%), and grade 1/2 hand-foot syndrome in three (14%). Other toxicities were uncommon. There was no treatment related death. Four (29%) PRs and seven (50%) SD were observed among 14 evaluable patients. Responses were seen in patients with renal (n = 1), gastric (n = 2) and pancreatic (n = 1) cancer.

CONCLUSIONS: These results demonstrate that CAP, DOC and OX can be safely combined at clinically relevant doses and this regimen merits further evaluation.