A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer.

ABSTRACT

OBJECTIVES: To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with oxaliplatin (L-OHP) as first-line treatment of patients with advanced breast (ABC) and non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-two patients (26 with NSCLC and 26 with ABC), who had not received prior chemotherapy for metastatic disease, were enrolled. The patients' median age was 64 years, and 42 (71%) had a performance status (WHO) 0-1. Docetaxel was given as a 1-hour infusion after standard premedication on day 1 and L-OHP as a 2 to 6-hour infusion on day 2 every 3 weeks. Doses were escalated at increments of 10 mg/m2. RESULTS: The DLT1 was reached at the doses of docetaxel 75 mg/m2 and L-OHP 80 mg/m2. The addition of rhG-CSF permitted further dose escalation (DLT2 docetaxel 90 mg/m2 and L-OHP 130 mg/m2). The dose-limiting events were grade 4 neutropenia, febrile neutropenia, grades 3 or 4 diarrhea and grade 3 fatigue. Out of 239 delivered cycles, grades 3 or 4 neutropenia occurred in 22 (9%) cycles with 5 (2%) neutropenic febrile episodes. There was one septic death. Grades 3 or 4 fatigue was observed in seven (13%) patients and grades 3-4 diarrhea in five (10%). Out of 42 patients evaluable for response, seven (27%) patients with ABC and five (19%) patients with NSCLC experienced a partial response. CONCLUSION: The combination of docetaxel and oxaliplatin is a feasible and well-tolerated regimen. The recommended doses for future phase II studies are 75 mg/m2 for docetaxel on day 1 and 70 mg/m2 for L-OHP on day 2 without rhG-CSF support and 85 mg/m2 and 130 mg/m2, respectively, with rhG-CSF support.