title: Induction cisplatin and paclitaxel followed by combination chemoradiotherapy with 5-fluorouracil, cisplatin, and paclitaxel before resection in localized esophageal cancer: a phase II report.
abstract: BACKGROUND
  Multimodality therapy for esophageal cancer holds promise for improving outcome in this lethal disease. On the basis of encouraging data from a phase I trial, we conducted a phase II study of preoperative chemotherapy, followed by concurrent chemoradiotherapy and surgery.
  
  
  METHODS
  Patients with clinically staged resectable esophageal cancer were treated with induction cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to eight weeks after multimodality induction, esophagectomy was performed in suitable patients. Study end points were survival, pathologic complete response, and toxicity.
  
  
  RESULTS
  Twenty-one patients were enrolled with a median age of 58 years, and all patients were clinically staged II or III. Sixteen (76.2%) patients completed the trial, of whom four (25%) had a pathologic complete response. One patient died from postoperative complications. Grade 3 or 4 toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in 6 of the first 14 patients, thus necessitating a planned dose reduction of paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2-year disease-specific survival for the study population was 78%.
  
  
  CONCLUSIONS
  This regimen of multimodality therapy before resection resulted in an encouraging 2-year survival rate but a disappointing rate of pathologic complete response and was toxic, necessitating a predetermined paclitaxel dose reduction. The incorporation of taxanes into induction strategies for esophageal cancer seems promising, but the optimal schedule remains undefined.
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Henry
authors.forename: Melvyn
authors.initials: M
authors.lastname: Goldberg
authors.forename: Walter
authors.initials: W
authors.lastname: Scott
authors.forename: Andre
authors.initials: A
authors.lastname: Konski
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Gary
authors.initials: G
authors.lastname: Freedman
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
authors.forename: Perry
authors.initials: P
authors.lastname: Watts
authors.forename: Mary
authors.initials: M
authors.lastname: Beard
authors.forename: Susan
authors.initials: S
authors.lastname: McLaughlin
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage; D011183:Postoperative Complications; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil