title: Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer.
abstract: BACKGROUND
  Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy.
  
  
  METHODS
  Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15-30 mg m(-2) per week and cisplatin 15-30 mg m(-2) per week in six planned dose levels (DLs) in 3-6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy.
  
  
  RESULTS
  A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m(-2), cisplatin 15 mg m(-2)) and grade 3 nausea in DL2 (20 mg m(-2), 15 mg m(-2)). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial).
  
  
  CONCLUSIONS
  Cisplatin and docetaxel each 30 mg m(-2) per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer.
authors.affiliation: Department of Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Melbourne, Victoria 8006, Australia.
authors.forename: F L
authors.initials: FL
authors.lastname: Day
authors.forename: T
authors.initials: T
authors.lastname: Leong
authors.forename: S
authors.initials: S
authors.lastname: Ngan
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Jefford
authors.forename: J R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: D
authors.initials: D
authors.lastname: Rischin
authors.forename: J
authors.initials: J
authors.lastname: McKendick
authors.forename: A D
authors.initials: AD
authors.lastname: Milner
authors.forename: J
authors.initials: J
authors.lastname: Di Iulio
authors.forename: A
authors.initials: A
authors.lastname: Matera
authors.forename: M
authors.initials: M
authors.lastname: Michael
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin