Enhanced antitumor efficacy of nedaplatin with 5-fluorouracil against human squamous carcinoma xenografts.
BACKGROUND
The antitumor efficacy of a combination of Nedaplatin (NDP) with 5-fluorouracil (5-FU) was evaluated using human squamous carcinomas in vivo. Because NDP was developed as a second generation platinum complex, we also compared the antitumor activity of NDP with 5-FU with that of Cisplatin (CDDP) with 5-FU.


METHODS
5-FU was injected daily for five days and either NDP or CDDP was injected once via the tail vein of mice implanted with KB3-1, OCC-1-JCK, LJC-1-JCK and Ma44 human squamous carcinomas. In some experiments, continuous administration of 5-FU using an osmotic pump was utilized.


RESULTS
The sequential administration of 5-FU prior to NDP or CDDP (FN or FC therapy) resulted in enhanced inhibition of tumor growth in comparison with NDP, CDDP or 5-FU monotherapy against KB3-1, OCC-1-JCK and LJC-1-JCK squamous carcinomas. The combination of FN treatment was synergistic and as effective as that of FC treatment. FN treatment with continuous infusion of 5-FU using an osmotic pump, also led to enhanced tumor growth inhibition and prolonged survival against Ma44 squamous carcinoma.


CONCLUSIONS
The results demonstrated the antitumor efficacy NDP with 5-FU against four human squamous carcinoma xenografts and suggested the clinical effectiveness of FN treatment.
Takeda
Y
Y
Shionogi Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
Kasai
H
H
Uchida
N
N
Yoshida
H
H
Maekawa
R
R
Sugita
K
K
Yoshioka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D013997:Time Factors
D009944:Organoplatinum Compounds; C053989:nedaplatin; D002945:Cisplatin; D005472:Fluorouracil