title: Phase I study of intraperitoneal irinotecan in patients with gastric adenocarcinoma with peritoneal seeding.
abstract: OBJECTIVE
  The objectives of this phase I study were to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary efficacy of intraperitoneally administered irinotecan (CPT-11) in gastric cancer patients with peritoneal seeding.
  
  
  METHODS
  Gastric adenocarcinoma patients with surgical biopsy proven peritoneal seeding were enrolled at the time of surgery. Prior to IP chemotherapy, patients underwent palliative gastrectomy and CAPD catheter insertion in which CPT-11 was administered on postoperative day 1. The IP CPT-11 was initiated at 50 mg/m(2), which was escalated to 100, 150, 200, 250, and 300 mg/m(2). IP CPT-11 chemotherapy was repeated every 3 weeks.
  
  
  RESULTS
  Seventeen patients received a total of 56 cycles at five different CPT-11 dose levels. The DLTs were neutropenic fever, neutropenia, and diarrhea. At the dose level 2 (100 mg/m(2)), there were one DLTs in one of the first cohort of three patients, but no DLTs at the second cohort of this level. At the dose level 5 (250 mg/m(2)), two DLTs were detected in the first two patients; thus, the accrual was stopped resulting in the recommended dose of IP CPT-11 of 200 mg/m(2). Median progression-free survival was 8.6 months (95% CI, 5.9,11.2), and median overall survival was 15.6 months (95% CI, 8.4,22.8). Pharmacokinetic results of the study showed that the C (max) of peritoneal SN-38 was achieved earlier than that of plasma SN-38.
  
  
  CONCLUSIONS
  Intraperitoneally administered CPT-11 was feasible and tolerable. Further, phase II study of IP CPT-11 in gastric cancer patients with peritoneal seeding is warranted.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
authors.forename: Moon Ki
authors.initials: MK
authors.lastname: Choi
authors.forename: Byung-Jin
authors.initials: BJ
authors.lastname: Ahn
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Yim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Sohn
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Noh
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Heo
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D005743:Gastrectomy / Q000379:methods; D006801:Humans; D007263:Infusions, Parenteral; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin