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A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors.
Hong, D S; Kurzrock, R; Naing, A; Wheler, J J; Falchook, G S; Schiffman, J S; Faulkner, N; Pilat, M J; O'Brien, J; LoRusso, P.
Afiliación
  • Hong DS; University of Texas M.D. Anderson Cancer Center, Unit 455, PO Box 301402, Houston, TX, 77030, USA, dshong@mdanderson.org.
Invest New Drugs ; 32(3): 436-44, 2014 Jun.
Article en En | MEDLINE | ID: mdl-24258465
The aim of this study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of E7107 in patients with advanced solid tumors. Patients in this phase I, open-label, single-arm, dose-escalation study had metastatic or locally advanced solid tumors and received E7107 as a 30-minute intravenous infusion at doses of 0.6, 1.2, 1.8, 2.4, 3.2, 4.3, and 5.7 mg/m(2). Twenty-six patients were enrolled in the study. At 5.7 mg/m(2), two patients experienced dose-limiting toxicities including diarrhea, vomiting, dehydration, and myocardial infarction on Days 1-3 following E7107 administration. Three additional patients were recruited at the lower dose and all six patients tolerated E7107 4.3 mg/m(2) with no dose-limiting toxicities. The maximum tolerated dose of E7107 was therefore 4.3 mg/m(2). The most common drug-related adverse events were nausea, vomiting, and diarrhea. Vision loss was experienced by two patients at Cycles 2 and 7, each patient receiving 3.2 mg/m(2) and 4.3 mg/m(2), respectively. This resulted in the study being put on clinical hold. Pharmacokinetic analysis showed that E7107 was rapidly distributed with a moderate elimination half-life (6-13 h) and high clearance. Exposure to E7107 was dose-related. The best tumor response was stable disease in eight patients. E7107 is a unique first-in-class molecule. The incidence of two cases of vision loss probably related to E7107 led to study discontinuation.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Macrólidos / Compuestos Epoxi / Neoplasias / Antineoplásicos Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Invest New Drugs Año: 2014 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Macrólidos / Compuestos Epoxi / Neoplasias / Antineoplásicos Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Invest New Drugs Año: 2014 Tipo del documento: Article