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

Ann Oncol. 2011 Jan;22(1):175-180. doi: 10.1093/annonc/mdq298. Epub 2010 Jun 7.

Abstract

Background: we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC).

Patients and methods: treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks.

Results: forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%.

Conclusions: TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Young Adult

Substances

  • Drug Combinations
  • Taxoids
  • S 1 (combination)
  • Tegafur
  • Docetaxel
  • Oxonic Acid
  • Cisplatin