Antitumor efficacy of nedaplatin, a novel platinum complex, with cyclophosphamide in murine and human tumor model.
BACKGROUND
The antitumor efficacy of the combination of Nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using murine and human carcinoma implanted mice. NDP was developed as a second generation platinum complex. Because of its superior antitumor activity and lower nephrotoxicity than Cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM.


METHODS
Various doses of NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) and CPM (58 or 78 mg/kg) were injected once via the tail vein into mice implanted with Lewis murine lung carcinoma or Ma44 human lung carcinoma.


RESULTS
Simultaneous administration of NDP or CDDP with CPM resulted in synergistically enhanced inhibition of tumor growth and prolonged survival in comparison with therapy using only NDP, CDDP or CPM. The combination therapy of NDP with CPM showed a superior survival effect with frequent long-term tumor-free survivors in comparison to that of CDDP plus CPM without increased hematotoxicity. The augmented antitumor efficacy of the combination of NDP with CPM was also demonstrated against Ma44 human lung carcinoma.


CONCLUSIONS
The results suggested the effectiveness of using a combination of NDP with CPM for clinical therapy.
Uchida
N
N
Discovery Research Laboratories II, Shionogi and Co., Ltd., Osaka, Japan.
Takeda
Y
Y
Kasai
H
H
Maekawa
R
R
Sugita
K
K
Yoshioka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology
D009944:Organoplatinum Compounds; D003520:Cyclophosphamide; C053989:nedaplatin; D002945:Cisplatin