A phase I trial of 5-fluorouracil with cisplatin and concurrent standard-dose radiotherapy in Japanese patients with stage II/III esophageal cancer

Jpn J Clin Oncol. 2009 Jan;39(1):37-42. doi: 10.1093/jjco/hyn125.

Abstract

Objective: In Japan, 5-fluorouracil (5-FU) 400 mg/m(2) on Days 1-5, 8-12, 36-40 and 43-46 with cisplatin (CDDP) 40 mg/m(2) on Days 1, 8, 36 and 43 plus concurrent radiotherapy with 2 weeks planned interruption (60 Gy) was standard for the patients with esophageal cancer. This Phase I trial was designed to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of 5-FU on Days 1-4 and 29-32 with CDDP on Days 1 and 29 plus concurrent radiotherapy (50.4 Gy) among the Japanese.

Methods: Escalating doses of 5-FU and CDDP were administered with concurrent radiotherapy (50.4 Gy). Treatment was continued until DLT appeared.

Results: Twelve patients with previously untreated clinical Stage II/III squamous cell esophageal carcinoma were studied. One of six patients given Level 1 (5-FU 800 mg/m(2) on Days 1-4 and 29-32 with CDDP 75 mg/m(2) on Days 1 and 29) developed a DLT of incomplete protocol treatment due to Grade 3 esophagitis. The MTD was not reached at Level 2 (5-FU 1000 mg/m(2) with CDDP 75 mg/m(2)). The complete response rate was 67% at Level 1 and 100% at Level 2.

Conclusions: Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanese patients.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Adenosquamous / drug therapy
  • Carcinoma, Adenosquamous / radiotherapy
  • Carcinoma, Adenosquamous / secondary
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / secondary
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / radiotherapy*
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Japan
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging

Substances

  • Cisplatin
  • Fluorouracil