title: Preoperative therapy with concurrent paclitaxel/carboplatin/infusional 5-FU and radiation therapy in locoregional esophageal cancer: final results of a Minnie Pearl Cancer Research Network phase II trial.
abstract: OBJECTIVE
  This phase II study was designed to determine the feasibility, toxicity, and therapeutic efficacy of a novel outpatient combined-modality preoperative regimen in patients with localized esophageal cancer.
  
  
  METHODS
  One hundred twenty-nine eligible patients with previously untreated, potentially resectable, clinical stage I-III carcinoma of the esophagus were treated between July 1995 and July 1999. Combined-modality treatment included: paclitaxel, 200 mg/m2, 1-hour i.v. infusion, days 1 and 22; carboplatin, an area under the concentration time curve 6.0 i.v., days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous i.v. infusion, days 1-42; and radiation therapy, 45 Gy, 1.8-Gy single daily fractions 5 days weekly, beginning day 1. All patients underwent surgical resection 4-8 weeks after completion of the preoperative therapy.
  
  
  RESULTS
  One hundred twenty-three patients (95%) completed preoperative therapy, 105 patients (81%) underwent attempted resection, and 96 patients (74%) had definitive resection. A pathological complete response was achieved in 47 of 123 evaluable patients (38%); an additional 30 patients (24%) had only microscopic residual tumor. With a median follow-up of 45 months, the median survival is 22 months (95% CI = 15-32 months), with actuarial 1-, 2-, and 3-year survivals of 71%, 47%, and 41%, respectively. The most frequent grade 3/4 toxicities of the neoadjuvant program were leukopenia (73%) and esophagitis (43%). Although 73 patients (57%) required brief hospitalizations during preoperative therapy, there were no treatment-related deaths, and 94% of patients remained candidates for resection after the completion of treatment. Six patients (6%) died after surgery.
  
  
  CONCLUSIONS
  This novel combined-modality regimen is highly active in the treatment of locoregional esophageal cancer, producing an actuarial 3-year survival of 41%. Although this preoperative regimen produced moderate acute toxicity, there were no treatment-related deaths and the large majority of patients were able to undergo subsequent esophageal resection. These results, obtained in a community-based setting and involving multiple surgeons, radiation oncologists, and medical oncologists, compare favorably with those of previous single-center and multicenter results. Further evaluation of novel combined-modality programs is warranted, as is the incorporation of epidermal growth factor receptor antagonists or other targeted agents.
authors.affiliation: Sarah Cannon Cancer Center, Nashville, Tennessee 37203, USA.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Meluch
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: James R
authors.initials: JR
authors.lastname: Gray
authors.forename: Melodie
authors.initials: M
authors.lastname: Thomas
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Sutton
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Kalman
authors.forename: Don W
authors.initials: DW
authors.lastname: Shaffer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Yost
authors.forename: David A
authors.initials: DA
authors.lastname: Rinaldi
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; 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; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D005472:Fluorouracil