title: Closed abdomen hyperthermic intraperitoneal chemotherapy with irinotecan and mitomycin C: a phase I study.
abstract: OBJECTIVE
  Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now a recognized treatment for peritoneal carcinomatosis (PC). The objective of this phase I study is to determine the maximum tolerated dose of irinotecan (CPT-11) when used with mitomycin C (MMC) for closed abdomen HIPEC.
  
  
  METHODS
  Patients with PC fulfilling the inclusion criteria were studied. All underwent cytoreductive surgery and closed abdomen HIPEC with 0.7 mg/kg MMC and an escalating dose of irinotecan. Grade 4 (National Cancer Institute grading system) surgical and hematological complications were used to identify dose-limiting toxicity (DLT).
  
  
  RESULTS
  12 patients were studied. At the first dose level of irinotecan (100 mg/m(2)), one patient developed a grade 4 hematological toxicity. Three other patients were included at the same level with no toxicity. Three patients were then included at the second dose level (150 mg/m(2) irinotecan), of whom one developed a grade 4 surgical complication. Three further patients were thus included at the second dose level. Of these three, two patients developed DLT [grade 4 neutropenia in one, grade 4 neutropenia and thrombocytopenia with an intra-abdominal lymphatic fistula requiring reoperation (grade 4 surgical complication) in the other]. Dose escalation was stopped at this level. The maximum tolerated dose of irinotecan was determined to be 100 mg/m(2).
  
  
  CONCLUSIONS
  Closed HIPEC combining MMC and irinotecan is safe and feasible. For HIPEC, the maximum tolerated dose of irinotecan is 100 mg/m(2) when used with 0.7 mg/kg MMC.
authors.affiliation: Department of Digestive Surgery, Centre Hospitalo-Universitaire Lyon Sud, Hospices Civils de Lyon, Pierre Bénite cedex, France. eddy.cotte@chu-lyon.fr
authors.forename: Eddy
authors.initials: E
authors.lastname: Cotte
authors.forename: Guillaume
authors.initials: G
authors.lastname: Passot
authors.forename: Michel
authors.initials: M
authors.lastname: Tod
authors.forename: Naoual
authors.initials: N
authors.lastname: Bakrin
authors.forename: François-Noël
authors.initials: FN
authors.lastname: Gilly
authors.forename: Aline
authors.initials: A
authors.lastname: Steghens
authors.forename: Faheez
authors.initials: F
authors.lastname: Mohamed
authors.forename: Olivier
authors.initials: O
authors.lastname: Glehen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016685:Mitomycin; D000077146:Irinotecan; D002166:Camptothecin