Cancer Chemotherapy and Pharmacology

, Volume 67, Issue 1, pp 5–11

Phase I study of intraperitoneal irinotecan in patients with gastric adenocarcinoma with peritoneal seeding

  • Moon Ki Choi
  • Byung-Jin Ahn
  • Dong-Seok Yim
  • Young Suk Park
  • Sung Kim
  • Tae Sung Sohn
  • Jae Hyung Noh
  • Jin Seok Heo
  • Jeeyun Lee
  • Se Hoon Park
  • Joon Oh Park
  • Ho Yeong Lim
  • Won Ki Kang
Original Article

DOI: 10.1007/s00280-010-1272-6

Cite this article as:
Choi, M.K., Ahn, B., Yim, D. et al. Cancer Chemother Pharmacol (2011) 67: 5. doi:10.1007/s00280-010-1272-6

Abstract

Purpose

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.

Experimental design

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/m2, which was escalated to 100, 150, 200, 250, and 300 mg/m2. 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/m2), 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/m2), 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/m2. 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 Cmax 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.

Keywords

Gastric adenocarcinomaPeritoneal seedingIrinotecanIntraperitoneal administration

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Moon Ki Choi
    • 1
  • Byung-Jin Ahn
    • 2
  • Dong-Seok Yim
    • 3
  • Young Suk Park
    • 1
  • Sung Kim
    • 4
  • Tae Sung Sohn
    • 4
  • Jae Hyung Noh
    • 4
  • Jin Seok Heo
    • 4
  • Jeeyun Lee
    • 1
  • Se Hoon Park
    • 1
  • Joon Oh Park
    • 1
  • Ho Yeong Lim
    • 1
  • Won Ki Kang
    • 1
  1. 1.Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  2. 2.Medical Science Research CenterDongguk UniversitySeoulKorea
  3. 3.Department of Pharmacology, College of MedicineThe Catholic University of KoreaSeoulKorea
  4. 4.Department of Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea