Cancer chemotherapy and pharmacology
-
Cancer Chemother. Pharmacol. · May 2008
Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand.
ECO-4601 is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER technology, Thallion's proprietary drug discovery platform. The compound was shown to have a broad cytotoxic activity in the low micromolar range when tested in the NCI 60 cell line panel. In the work presented here, ECO-4601 was further evaluated against brain tumor cell lines. Preliminary mechanistic studies as well as in vivo antitumor evaluation were performed. ⋯ Antitumor efficacy of ECO-4601 appears to be associated with the exposure parameter AUC and/or sustained drug levels rather than C (max). These in vivo data constitute a rationale for clinical studies testing prolonged continuous administration of ECO-4601.
-
Cancer Chemother. Pharmacol. · May 2008
Phase-1 trial of gefitinib and temozolomide in patients with malignant glioma: a North American brain tumor consortium study.
This is a phase-I study of gefitinib in combination with temozolomide in patients with gliomas. The goal of the study was to define the maximum tolerated dose (MTD) and to characterize the pharmacokinetics of gefitinib when combined with temozolomide. ⋯ The recommended phase-2 dose of gefitinib when used in combination with temozolomide is 1,000 and 250 mg/day, respectively, for patients on or not on EIAEDs.