Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF-CRT) for locally advanced squamous cell carcinoma of the external auditory canal

Purpose Chemoradiotherapy with docetaxel (DOC), cisplatin (CDDP), and 5-FU (TPF-CRT) for locally advanced external auditory canal cancer (EACC) has favorable oncological and functional outcomes. To establish TPF-CRT as a standard of care for advanced EACC, we conducted this study to determine the maximum tolerated (MTD) and recommended dose (RD) of DOC in TPF-CRT for locally advanced EACC. Methods To determine the recommended (RD) and maximum tolerated dose (MTD) of DOC in TPF-CRT for EACC, a phase I trial was conducted using the standard “3 + 3” design for maximum dose finding. DOC was administered twice every 4 weeks, CDDP at 70 mg/m 2 and 5-FU at 700 mg/m 2 ; patients were also receiving radiotherapy (66 Gy). Eight patients with T3 or T4 EACC were prospectively enrolled. Results Two patients treated with DOC, 50 mg/m 2 , and one out of six patients treated with DOC, 40 mg/m 2 , had dose-limiting toxicities. Prolonged febrile neutropenia was observed in three patients. Grade 3 non-hematological toxicities were observed in only three patients. At study completion, six patients survived, five of whom were disease free. Conclusion The RD and MTD of DOC in TPF-CRT for locally advanced EACC are 40 mg/m 2 when doses of CDDP and 5-FU are 70 mg/m 2 and 700 mg/m 2 , respectively.