Phase I trial of chemotherapy combination with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/ metastatic head and neck cancer (HNC)

Abstract

6064 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC) with a response rate of 34% and preclinical data has demonstrated a possible synergy with platinums and taxanes. The aim of this study was to determine the maximum tolerated dose (MTD) of a combination therapy with TPS in patients (pts) with locally advanced or recurrent/ metastatic HNC. Methods: The eligibility criteria were: histologically proven squamous cell carcinoma of the head and neck with recurrent/metastatic and locally advanced lesions, PS 0–1, age =75 years, adequate organ function, and no prior chemotherapy. Chemotherapy consisted of 1-hour infusion of docetaxel at escalating doses of 50 and 60 mg/m2, 2-hour infusions of cisplatin at 70 mg/m2/day on day 1 and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. The treatment was repeated every 4-weeks. Results: Twenty two pts were enrolled. These were 17 males and 5 females with a median age of 50 years (22–74). There were 11 locally advanced and 11 metastatic cases. Median of 3 cycles were administrated (range 1–6; total 77 cycles). Anorexia, nausea, neutropenia and anemia were the most frequently observed adverse events. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (0%), anemia (14%) and thrombocytopenia (0%). Although a total of 12 pts were treated with TPS at doses of 60/70/80 mg/m2/day, one-dose limiting toxicity (grade3 infection) was observed at these doses, but MTD was not reached. As the approved dose of S-1 is 80 mg/m2, further dose escalation was not conducted. In a total of 22 pts treated with the TPS, 3 (1 locally advanced, 2 metastatic cases) achieved complete response and 11 (7 locally advanced, 4 metastatic cases) achieved partial response according to RECIST with an overall response rate of 64%. Conclusions: The TPS combination was well tolerated in pts with locally advanced or recurrent/ metastatic HNC. Although MTD was not reached and the data were preliminary, the antitumor activity was very promising, and this warrants further investigation. No significant financial relationships to disclose.