Phase I study of intraperitoneal irinotecan in patients with gastric adenocarcinoma with peritoneal seeding.
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.
Choi
Moon Ki
MK
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Ahn
Byung-Jin
BJ
Yim
Dong-Seok
DS
Park
Young Suk
YS
Kim
Sung
S
Sohn
Tae Sung
TS
Noh
Jae Hyung
JH
Heo
Jin Seok
JS
Lee
Jeeyun
J
Park
Se Hoon
SH
Park
Joon Oh
JO
Lim
Ho Yeong
HY
Kang
Won Ki
WK
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
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin