[Combination therapy of a new platinum complex, DWA2114R with various antitumor agents against mouse tumors in vivo].
In vivo antitumor activity of (-)-(R)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) monohydrate (DWA2114R) in combination with various antitumor agents was examined using mouse leukemia P388, Meth-A fibrosarcoma and M5076 reticulum cell sarcoma. The combination treatment of DWA2114R with cyclophosphamide, 5-fluorouracil, adriamycin, etoposide or vindesine showed synergistic effects on the prolongation of survival time of mice bearing P388. Among these combinations, combination of DWA2114R with adriamycin or vindesine showed a good synergism. In the combination treatment with vindesine against Meth-A which is not so sensitive to platinum agent, DWA2114R showed a synergistic or additive effect, but cis-diamminedichloroplatinum (II) (CDDP) showed subadditive. Three-drug combination of DWA2114R or CDDP with cyclophosphamide and adriamycin was examined in mice inoculated i.p. or s.c. with M5076. In both models, the combination of DWA2114R was more active than that of CDDP at the dose less than 1/16-fold of the dose of CDDP which is the ratio of two drugs in clinical trial.
Akamatsu
K
K
Exploratory Research Laboratories, Chugai Pharmaceutical Co. Ltd., Japan.
Endo
K
K
Tsunenari
T
T
Matsumoto
T
T
Kaiho
S
S
Morikawa
K
K
Koizumi
M
M
Mitsui
H
H
Koizumi
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D005472:Fluorouracil / Q000008:administration & dosage; D007941:Leukemia P388 / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010051:Ovarian Neoplasms / Q000188:drug therapy; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D014751:Vindesine / Q000008:administration & dosage
C058816:DWA 2114; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D014751:Vindesine; D005472:Fluorouracil