Cytotoxicity of CPT-11 and SN-38 for gastrointestinal and recurrent carcinomas cultured on contact-sensitive plates.
CPT-11 is a derivative of camptothecin, a topoisomerase-I inhibitor with marked cytotoxic activity. We examined the cytotoxicity of CPT-11 and its metabolite SN-38 for primary gastrointestinal carcinoma and various recurrent carcinomas which were cultured on contact-sensitive plates (CSPs). The response rate of seven gastrointestinal carcinomas for either CPT-11 or SN-38 was 71% (5/7). The response was higher than those for other anticancer agents, including adriamycin (ADM), cisplatinum (CDDP) and 5-fluorouracil (5-FU). The mean percent survival of these tumor cells was 69% when incubated with 25 ng/ml of SN-38, which was the lowest survival for all the anticancer drugs tested. IN the case of recurrent carcinomas, the response rate to either CPT-11 or SN-38 was 60% (3/5), and was higher than the rates for MMC, CDDP or 5-FU. The mean percent survival of the recurrent carcinoma cells was 76% in the presence of 25 ng/ml SN-38, and this was once again the lowest survival rate. CPT-11 had a stronger inhibitory effect against one carcinoma than SN-38 when a clinical drug concentration was added to the culture medium, suggesting that CPT-11 itself was cytotoxic. IN addition, one carcinoma with a low response to CDDP also showed no response to CPT-11, but was very occurred because of decreased conversion of CPT-11 to SN-38. Our results suggest that CPT-11 may be a useful agent for the treatment of both primary gastrointestinal cancer and various recurrent carcinomas.
Matsuoka
H
H
Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan.
Furusawa
M
M
Tomoda
H
H
Seo
Y
Y
Kono
A
A
Takeda
S
S
Sato
K
K
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell; D002430:Cecal Neoplasms / Q000473:pathology*; D002460:Cell Line; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007890:Leiomyosarcoma / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000473:pathology*; D012008:Recurrence; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin