title: Phase I trial of 5-FU, docetaxel, and nedaplatin (UDON) combination therapy for recurrent or metastatic esophageal cancer.
abstract: OBJECTIVE
  The aims of this dose-escalating phase I study were to determine the maximum tolerable dose (MTD) and recommended dose (RD) of 5-fluorouracil (5-FU), docetaxel, and nedaplatin (UDON) combination therapy for future phase II studies, and to evaluate the safety and efficacy of this regimen in patients with untreated recurrent or metastatic esophageal cancer.
  
  
  METHODS
  Patients were administered 5-FU on days 1-5, docetaxel on days 1 and 15, and nedaplatin on day 1 at 4-week intervals. The dose levels of 5-FU/docetaxel/nedaplatin were escalated as follows (mg/m(2)): level 1, 800/30/80; level 2, 800/30/90; and level 3, 800/35/90. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0.
  
  
  RESULTS
  Overall, nine patients were enrolled in this study. All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 and were diagnosed with squamous cell carcinoma. No dose-limiting toxicity was observed at any level, and planned dose escalation was completed without reaching the MTD. No grade 4 or higher toxicity was observed in this study. The observed grade 3 hematological toxicities included neutropenia in five patients (55.6 %) and leukopenia in three patients (33.3 %). None of the patients developed febrile neutropenia, and no grade 3 or 4 non-hematological toxicities were observed. The overall response rate was 77.8 %, including two complete responses, and the disease control rate was 100 %.
  
  
  CONCLUSIONS
  The RD of UDON was identified as level 3. The good tolerability and high antitumor efficacy of this regimen warrant further evaluation in this setting.
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Kinki University, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueda
authors.forename: Hisato
authors.initials: H
authors.lastname: Kawakami
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishina
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Nonagase
authors.forename: Takafumi
authors.initials: T
authors.lastname: Okabe
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C053989:nedaplatin; D005472:Fluorouracil