Phase I/II docetaxel plus concurrent hyperfractionated radiotherapy in locally advanced unresectable head and neck cancer (TAX.ES1.102 study).
INTRODUCTION
Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer.


OBJECTIVE
The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS).


MATERIALS AND METHODS
Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m(2) plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m(2) if MTD was not reached.


RESULTS
MTD of docetaxel was 20 mg/m(2). Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m(2). Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0-22.3) and the median OS was 15.1 months (95%CI: 0-35.9). Grade 3-4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia).


CONCLUSIONS
Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify.