Phase I/II study of s-1 plus cisplatin combination chemotherapy in patients with advanced/recurrent head and neck cancer

Jpn J Clin Oncol. 2010 Mar;40(3):214-21. doi: 10.1093/jjco/hyp153. Epub 2009 Nov 23.

Abstract

Objective: The objectives of this study were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus cisplatin (CDDP) and to evaluate safety and efficacy using the defined RD in advanced/recurrent head and neck cancer (HNC).

Methods: S-1 was administered orally at 40 mg/m(2) twice daily for 14 consecutive days, and CDDP was infused on day 8 at a dose of 60 and 70 mg/m(2). Each course was repeated every 4 weeks.

Results: A total of 38 patients were registered, 10 patients for the Phase I study and an additional 28 patients for the Phase II study. Although no dose-limiting toxicity (DLT) was observed in the CDDP 60 mg/m(2) (Level 1) group, two of six patients in the CDDP 70 mg/m(2) (Level 2) group exhibited DLT (fatigue/diarrhea). The MTD was not achieved in the Phase I study. Level 2 was therefore determined as the RD. In the Phase II study, 34 patients, including 6 patients from the Phase I study, were evaluated. At the termination of treatment, the confirmed response rate was 44.1% (15/34, 95% CI: 27.4-60.8). The best response rate without an adequate duration time was 67.6% (95% CI: 51.9-83.4). The median survival period was 16.7 months, and the 1-year survival rate was 60.1%. The main toxicities of Grade 3 or above were anorexia (26.5%), nausea (14.7%), neutropenia/thrombocytopenia (11.8%) and anemia/fatigue (8.8%).

Conclusions: This is considered to be an effective regimen with acceptable toxicities for HNC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / secondary
  • Cisplatin / administration & dosage
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Infusions, Intravenous
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Oxonic Acid / administration & dosage
  • Prognosis
  • Survival Rate
  • Tegafur / administration & dosage
  • Treatment Outcome
  • Young Adult

Substances

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