title: Preoperative hyperfractionated accelerated radiotherapy (HART) and concomitant CPT-11 in locally advanced rectal carcinoma: a phase I study.
abstract: OBJECTIVE
  Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect.
  
  
  METHODS
  Twenty-eight patients (19 males; median age 63, range 28-75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN+: 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30-105 mg/m(2)/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid x 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy.
  
  
  RESULTS
  Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m(2)). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%.
  
  
  CONCLUSIONS
  The recommended Phase II dose of CPT-11 in this setting is 90 mg/m(2)/week. Further Phase II exploration at this dose is warranted.
authors.affiliation: Multidisciplinary Oncology Center, University Hospital CHUV, Lausanne, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Voelter
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Maurice
authors.initials: M
authors.lastname: Matter
authors.forename: Michel
authors.initials: M
authors.lastname: Gillet
authors.forename: Hanifa
authors.initials: H
authors.lastname: Bouzourene
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
authors.forename: Philippe
authors.initials: P
authors.lastname: Coucke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology; D012004:Rectal Neoplasms / Q000628:therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin