Sequence-dependent antitumor efficacy of combination chemotherapy with nedaplatin, a newly developed platinum, and paclitaxel.
We evaluated the sequence dependency of antitumor efficacy and toxicity in combination therapy of nedaplatin (NDP) with paclitaxel (TXL) against Lewis lung carcinoma. The sequential administration of NDP prior to TXL (NT therapy) resulted in severe body weight loss followed by frequent toxic death of mice. In contrast, the sequential dosing of TXL prior to NDP (TN therapy) resulted in synergistically enhanced inhibition of tumor growth with less toxicity compared with the NT therapy. Comparing the antitumor activity of NDP plus TXL with that of cisplatin (CDDP) plus TXL or carboplatin (CBDCA) plus TXL, the combination effect of NDP plus TXL was significantly higher than that of CDDP plus TXL or CBDCA plus TXL. These results indicate that the TN therapy may have significant potential in clinical use.
Yamada
H
H
Discovery Research Labs, Shionogi Research Laboratories, Shionogi & Co., Ltd, 12-4 Sagisu, 5-chome, Fukusima-ku, Osaka 552-0002, Japan.
Uchida
N
N
Maekawa
R
R
Yoshioka
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D008099:Liver / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D013997:Time Factors
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; C053989:nedaplatin; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin