title: A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohnuma
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okagawa
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osuga
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Miyanishi
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.affiliation: Division of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sagawa
authors.affiliation: Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Someya
authors.affiliation: Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Department of Gastroenterology and Oncology, University of Tokushima, Tokushima, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: jkato@sapmed.ac.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000401:mortality / Q000628:therapy*; D004941:Esophagitis / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011014:Pneumonia / Q000209:etiology; D011879:Radiotherapy Dosage; D013280:Stomatitis / Q000209:etiology; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C053989:nedaplatin; D005472:Fluorouracil