title: [Phase I study of the combination of nedaplatin (NED), adriamycin (ADM), and 5-fluorouracil (5-FU) (NAF) for treatment of unresectable advanced esophageal cancer].
abstract: BACKGROUND
  Esophageal cancer has a poor prognosis. Several strategies including chemotherapy (CDDP+5-FU), either alone or with radiotherapy, have been used to improve the prognosis. However, since CDDP itself has substantial toxicities, including renal and gastrointestinal toxicities, newer platinum analogues, such as nedaplatin (NED) have been developed, and it is of interest to test this new platinum analogue in a combination chemotherapy.
  
  
  METHODS
  We conducted a phase I-II study using a combination of NED (3 levels, 60-80 mg/m2 on day 1), ADM (30 mg/m2 on day 1), and 5 FU (700 mg/m2 on day 1-5) for treatment of previously untreated advanced esophageal squamous cell carcinoma. Cycles were repeated every 28 days. The objectives were to determine dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), recommended dose (RD) for a phase II study, and to determine antitumor effects.
  
  
  RESULTS
  Phase I: 12 patients (pts) (male/female=11/1) were evaluable. The median age was 65 (range 46-74), PS 0/1=7/5. At level 1, 1 pt developed DLT (grade 4, neutropenia). At level 2, 2 pts developed DLT (grade 4 neutropenia and grade 3 diarrhea). Level 2 (70 mg/m2) was determined as the MTD, and a level 1 dose (60 mg/m2) was recommended. Phase II: 7 pts (male/female=4/3) are at RD of level 1 at the present time. Median age 62 (range 46-75). The median number of cycles on phase II study at RD was 2 (range 1-3). 4 PRs were obtained. The response rate was 57.1%. Median survival time (MST) was not reached at the time.
  
  
  CONCLUSIONS
  This combination therapy appears to be highly effective and generally well tolerated for advanced esophageal cancer.
authors.affiliation: Dept of Surgery, Osaka National Hospital.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hirao
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fujitani
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tsujinaka
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D004317:Doxorubicin; C053989:nedaplatin; D005472:Fluorouracil