Phase I-II study of irinotecan combined with mitomycin-C in patients with advanced gastric cancer.
BACKGROUND
Irinotecan (CPT-11) shows synergism with mitomycin-C (MMC) in a preclinical setting. The goals of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity, the recommended dose (RD), and preliminary anti-tumor activity in a combined CPT-11 and MMC treatment of advanced gastric cancer.


METHODS
The study was designed to evaluate escalated doses of CPT-11 and MMC administered every two weeks. Five escalating dose levels were studied (CPT-11/ MMC: 100/5; 125/5; 150/5; 150/7; 150/10 mg/m2).


RESULTS
Thirty-one patients were enrolled. Thirty patients were assessable for toxicity and tumor response for 89 treatment cycles. The median age was 60 years (32-73 years), and most patients (90%) had a performance status of 0 to 1. Fourteen patients were previously treated and 17 were chemotherapynaive. The MTD was CPT-11 150 mg/m2 plus MMC 10 mg/m2, in which all three patients experienced grade 4 neutropenia. including one episode of prolonged and one of febrile neutropenia, and one patient experienced grade 3 diarrhea during the first cycle. Fifteen partial responses were observed.


CONCLUSIONS
The RD based on this phase I-II study was CPT-11 150 mg/m2 plus MMC 5 mg/m2 administered every two weeks. This combination demonstrates promising activity against advanced gastric cancer and warrants further investigation in another phase II study.
Yamao
T
T
Department of Internal Medicine, Cancer Institute Hospital, Tokyo, National Cancer Center Hospital, Tokyo, Japan. tyamao-gi@umin.ac.jp
Shirao
K
K
Matsumura
Y
Y
Muro
K
K
Yamada
Y
Y
Goto
M
M
Chin
K
K
Shimada
Y
Y
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
D016685:Mitomycin; D000077146:Irinotecan; D002166:Camptothecin