Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours.

Abstract

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment