Combination effect of TZT-1027 (Soblidotin) with other anticancer drugs.
BACKGROUND
TZT-1027 (Soblidotin), an antimicrotubule drug, has shown potent antitumor efficacy in various antitumor models, and has entered into phase I clinical trials. To determine those anticancer drugs to be combined with TZT-1027 in clinical trials, the combination effects of TZT-1027 with other anticancer drugs were examined.


METHODS
Two in vivo antitumor models, the murine P388 leukemia ascites tumor model and the human non-small cell lung cancer A549 solid tumor model, were used and cisplatin (CDDP), gemcitabine (GEM), irinotecan hydrochloride (CPT-11), fluorouracil (5-FU), paclitaxel (PTX) and docetaxel (DTX) were selected to be combined with TZT-1027. Regarding the schedule of combination administration, simultaneous administration and sequential administration (TZT-1027 first and combined drugs administered 24 h later, and vice versa) were employed.


RESULTS
A significant increase in lifespan was observed when TZT-1027 was combined with CDDP, GEM and CPT-11 in the P388 cell ascites tumor model, and a significant inhibition of growth was observed when TZT-1027 was combined with CDDP, GEM and DTX in the A549 solid tumor model. Sequential administration, particularly when the combined drug was administered first, showed the most potent antitumor efficacy.


CONCLUSIONS
These findings strongly suggest that a significant combination effect of TZT-1027 and these antitumor drugs can be expected in clinical trials for solid tumors.
Natsume
Tsugitaka
T
ASKA Pharmaceutical Co., Ltd., R&D Administration, Kawasaki-shi, Kanagawa 213-8522, Japan. natsume-t@aska-pharma.co.jp
Watanabe
Jun-Ichi
J
Horiuchi
Toshi
T
Kobayashi
Motohiro
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D007941:Leukemia P388 / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
D009842:Oligopeptides; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000077146:Irinotecan; C105791:soblidotin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine