title: Phase I trial of capecitabine and weekly irinotecan in combination with radiotherapy for neoadjuvant therapy of rectal cancer.
abstract: OBJECTIVE
  To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer.
  
  
  METHODS
  Nineteen patients with rectal cancer clinical stage T3-4, Nx received weekly irinotecan 50 mg/m(2) (days 1, 8, 15, 22, 29) and two doses of capecitabine (days 1 through 38; dose level [DL] I, 500 mg/m(2) bid; DL II, 625 mg/m(2) bid) according to phase I methodology. Three-dimensional conformal RT was given to a dose of 50.4 Gy (45 Gy + 5.4 Gy).
  
  
  RESULTS
  On DL I, no dose-limiting toxicities occurred, whereas diarrhea grade 3 affected three of seven patients on DL II. Twelve patients were treated on DL I and received a median relative dose-intensity of 100% for both drugs. Grade 3 or 4 adverse events were observed in only one of these patients (asthenia grade 3). All patients underwent surgery and R0 resection was achieved in all patients. Pathologic complete remission was observed in four patients and another five patients had only microfoci of residual tumor.
  
  
  CONCLUSIONS
  Preoperative chemoradiotherapy with CAPIRI is feasible and well tolerated. The preliminary efficacy is good, and the tolerability is at least comparable with data for fluorouracil plus irinotecan chemoradiotherapy. Larger phase II trials of the CAPIRI-RT schedule clearly are warranted.
authors.affiliation: Onkologisches Zentrum, III Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer, D-68167 Mannheim, Germany. ralf.hofheinz@med3.ma.uni-heidelberg.de
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: Bolko
authors.initials: B
authors.lastname: von Gerstenberg-Helldorf
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gnad
authors.forename: Uta
authors.initials: U
authors.lastname: Kraus-Tiefenbacher
authors.forename: Albrecht
authors.initials: A
authors.lastname: Müldner
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Post
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Frank
authors.initials: F
authors.lastname: Willeke
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000633:toxicity; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000633:toxicity; D012004:Rectal Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin