[Augmented antitumor efficacy of combination chemotherapy of nedaplatin with 5-fluorouracil in in vivo murine and human tumor model].
Augmented antitumor activity was demonstrated in combination chemotherapy of Nedaplatin (NDP) or Cisplatin (CDDP) with 5-fluorouracil (5-FU) against murine lung carcinoma and human squamous carcinoma from head and neck. Either NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) was injected once and 5-FU (1/16 MTD) was injected daily for five days via tail vein to tumor-implanted mice. The sequential administration of either NDP or CDDP prior to 5-FU (NF or CF therapy) showed severe body weight loss followed by the toxic death of tumor-bearing mice at the MTD of NDP or CDDP. In contrast, the reverse sequence of the treatment, that is, 5-FU prior to NDP or CDDP (FN or FC therapy), resulted in the synergistically enhanced inhibition of tumor growth and the prolonged survival in comparison with NDP, CDDP or 5-FU monotherapy. The antitumor activities of the combinations of CDDP with 5-FU was less than those of the combination of NDP with 5-FU. Especially, at the MTD of NDP in FN therapy, long-term tumor-free survival was frequently observed. Thus, FN therapy was thought to be the most efficient regimen in combination of NDP with 5-FU as a clinical therapy.
Uchida
N
N
Discovery Research Laboratories, Shionogi & Co., Ltd.
Takeda
Y
Y
Kasai
H
H
Hojo
K
K
Wada
T
T
Nishida
K
K
Maekawa
R
R
Sugita
K
K
Yoshioka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; 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; D009944:Organoplatinum Compounds / Q000008:administration & dosage
D009944:Organoplatinum Compounds; C053989:nedaplatin; D005472:Fluorouracil