Effects of CPT-11 in combination with other anti-cancer agents in culture.
CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy camptothecin, is a newly developed water-soluble camptothecin derivative now undergoing phase-II evaluation. In an attempt to establish whether the combination of CPT-11 with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-11 in combination with 11 other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture. We used both CPT-11 and SN-38 (active substance of CPT-11 in vivo), for our study. Cells were incubated for 3 days in the presence of 2 drugs (CPT-11 or SN-38 and another drug) and cytotoxic effects were determined by MTT assay. The effects of drug combinations on ID50 were analyzed by an improved isobologram method. Supra-additive and marginal supra-additive effects (synergism) were observed for CPT-11 in combination with cisplatin, cytosine arabinoside and mitomycin C. Additive effects were observed for its combination with amsacrine, bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitoxantrone and vincristine. Alternate sub-additive and protective effects (antagonism) were observed for CPT-11 in combination with methotrexate. Similar tendencies were observed for SN-38 in combination with other agents. These results suggest that CPT-11 in simultaneous administration with a majority of anti-cancer agents has an advantage for cytokilling. Of these agents, cisplatin, cytosine arabinoside and mitomycin C are most suitable for simultaneous administration with CPT-11.
Kano
Y
Y
Division of Medical Oncology, Tochigi Cancer Center, Japan.
Suzuki
K
K
Akutsu
M
M
Suda
K
K
Inoue
Y
Y
Yoshida
M
M
Sakamoto
S
S
Miura
Y
Y
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin