Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer

BACKGROUND: Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy. METHODS: Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15-30 mg m(-2) per week and cisplatin 15-30 m gm(-2) per week in six planned dose levels (DLs) in 3-6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy. RESULTS: A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m(-2), cisplatin 15 mg m(-2)) and grade 3 nausea in DL2 (20 mg m(-2), 15 mg m(-2)). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial). CONCLUSION: Cisplatin and docetaxel each 30 mg m(-2) per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer. British Journal of Cancer (2011) 104, 265-271. doi: 10.1038/sj.bjc.6606051 www.bjcancer.com Published online 14 December 2010 (C) 2011 Cancer Research UK