A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):382-90. doi: 10.1016/j.ijrobp.2015.05.041. Epub 2015 Jun 3.

Abstract

Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R).

Methods and materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m(2)) and nedaplatin (50 mg/m(2)) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design.

Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m(2). In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months.

Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Disease-Free Survival
  • Docetaxel
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / therapy*
  • Esophagitis / etiology
  • Feasibility Studies
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neutropenia / etiology
  • Organoplatinum Compounds / administration & dosage
  • Pneumonia / etiology
  • Radiotherapy Dosage
  • Stomatitis / etiology
  • Taxoids / administration & dosage

Substances

  • Organoplatinum Compounds
  • Taxoids
  • Docetaxel
  • nedaplatin
  • Fluorouracil