title: Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer.
abstract: OBJECTIVE
  To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC).
  
  
  METHODS
  Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU 180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients.
  
  
  RESULTS
  Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses.
  
  
  CONCLUSIONS
  OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Nikhil I
authors.initials: NI
authors.lastname: Khushalani
authors.forename: Cynthia Gail
authors.initials: CG
authors.lastname: Leichman
authors.forename: Gary
authors.initials: G
authors.lastname: Proulx
authors.forename: Hector
authors.initials: H
authors.lastname: Nava
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodnar
authors.forename: Donald
authors.initials: D
authors.lastname: Klippenstein
authors.forename: Alan
authors.initials: A
authors.lastname: Litwin
authors.forename: Judy
authors.initials: J
authors.lastname: Smith
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Nava
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Pendyala
authors.forename: Patrick
authors.initials: P
authors.lastname: Smith
authors.forename: William
authors.initials: W
authors.lastname: Greco
authors.forename: Joanne
authors.initials: J
authors.lastname: Berdzik
authors.forename: Harold
authors.initials: H
authors.lastname: Douglass
authors.forename: Lawrence
authors.initials: L
authors.lastname: Leichman
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil