Combination chemotherapy with nedaplatin and cyclophosphamide in human ovarian cancer model.
The antitumor efficacy of the combination of nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using human ovarian cancer models. Since NDP has been found to have greater antitumor activity and lower nephrotoxicity than cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM. Increasing doses of NDP (16.5, 33 and 66 mg/kg as a total dose) and a fixed amount of CPM (174 or 348 mg/kg as a total dose) were injected three times at intervals of 7 days via the tail vein into mice implanted with RMUG-S, OC9-JCK or KF-28 human ovarian cancer. Simultaneous administration of NDP with CPM resulted in markedly enhanced inhibition of tumor growth for all cancers tested. The growth inhibition and survival effect of the combination therapy of NDP with CPM against KF-28 and OC9-JCK were as potent as those of CDDP plus CPM. Neither increased hematotoxicity nor a significant difference in maximum concentration, half time or area under the curve of platinum or CPM in plasma between the single and combined treatment was found. These results suggest that the combination of NDP with CPM may be clinically effective.
Uchida
N
N
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka.
Yoshida
H
H
Yamada
H
H
Wada
T
T
Daikatsu
K
K
Ikeuchi
I
I
Maekawa
R
R
Sugita
K
K
Yoshioka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D009944:Organoplatinum Compounds; D003520:Cyclophosphamide; C053989:nedaplatin; D002945:Cisplatin