A phase I/II trial of weekly docetaxel and cisplatin for locoregionally recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN)

Abstract

15523 Background: Docetaxel and cisplatin are both active agents in the treatment of advanced SCCHN. In phase II trials the combination of docetaxel and cisplatin delivered on a 3 weekly schedule in recurrent/metastatic SCCHN demonstrated response rates (RR) of 33–46%, however it is associated with significant morbidities and treatment related mortalities. In a phase IB trial design we sought to determine the maximal tolerated dose (MTD) and the recommended dose for weekly docetaxel and cisplatin to further study in a phase II trial. Methods: Patients with measurable locoregionally recurrent and/or metastatic SCCHN with no prior chemotherapy for advanced disease were eligible. Four dose levels were planned, starting with docetaxel 25 mg/m2 and cisplatin 20 mg/m2 weekly (dose level 1) to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 (dose level 4) for three consecutive weeks followed by a one week break (=1 cycle). Pharmacokinetics (PK) were performed during cycle 1 and 2. Response was assessed following every 2nd cycle. Patients were followed for safety, tolerability, duration of response and survival. Results: 16 patients were enrolled from Aug 2003-Oct 2005. 80% were male, median age 61 years (36–72), median PS 1 (0–2), 30% had prior platinum exposure as a radio-sensitizer, and two-thirds had metastatic SCCHN. MTD was not achieved with dose level 4. Median number of cycles delivered was 3 (1–6) with no significant dose reductions or delays. No G3/4 hematological toxicities or febrile neutropenia was seen across all the dose levels. One G3 dysphagia, one G3 emesis and three G3 metabolic toxicities were seen. There was no treatment related deaths. 1 CR, 2 PR and 7 stable diseases were seen with a median duration of response/stable disease of 3 months (2–19). Conclusions: Combination weekly docetaxel and cisplatin is a well tolerated and active regimen in recurrent/metastatic SCCHN. The recommended dose is docetaxel 35 mg/m2 and cisplatin 25 mg/m2 (3 consecutive weeks out of 4) in the planned phase II trial. [Table: see text]