In vivo antitumour efficacy of MGI-114 (6-hydroxymethylacylfulvene, HMAF) in various human tumour xenograft models including several lung and gastric tumours.
MGI-114 (6-hydroxymethylacylfulvene, HMAF) is a semi-synthetic analogue of the cytotoxic sesquiterpenoid illudins. In the present study, the in vivo antitumour efficacy of MGI-114 was examined in a panel of human tumour xenograft models consisting mainly of human lung and gastric tumours, and compared with that of other antitumour drugs such as irinotecan, paclitaxel, cisplatin, doxorubicin, vindesine, etoposide and 5-fluorouracil (5-FU). When different administration schedules were compared, daily administration of MGI-114 was found to be more effective than intermittent administrations. In human tumour xenograft models of nasopharyngeal, breast and colon carcinoma and melanoma, MGI-114 exerted a strong antitumour activity with complete tumour regression being observed. Moreover, in four human lung and three gastric tumour xenograft models, MGI-114 showed a strong antitumour activity with complete tumour regression being observed in some of the models. The antitumour efficacy of MGI-114 was generally higher than or equivalent to that of other antitumour drugs such as irinotecan and paclitaxel. These results support the potential utility of MGI-114 in the treatment of a variety of human solid tumours.
Sato
Y
Y
Department of Pharmacology II, Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd. Enoki 33-94, Suita, 564-0053, Osaka, Japan. yuji-sato@dainippon-pharm.co.jp
Kashimoto
S
S
MacDonald
J R
JR
Nakano
K
K
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D012717:Sesquiterpenes / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D018906:Antineoplastic Agents, Alkylating; D012717:Sesquiterpenes; C102714:irofulven