MedStar Authors catalog › Details for: Obatoclax mesylate, a pan-bcl-2 inhibitor, in combination with docetaxel in a phase 1/2 trial in relapsed non-small-cell lung cancer.
Obatoclax mesylate, a pan-bcl-2 inhibitor, in combination with docetaxel in a phase 1/2 trial in relapsed non-small-cell lung cancer. Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.ISSN: 1556-0864.UI/PMID: 24346101.Subject(s): *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] | *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy] | Carcinoma, Non-Small-Cell Lung/mo [Mortality] | Humans | *Lung Neoplasms/dt [Drug Therapy] | Lung Neoplasms/mo [Mortality] | Maximum Tolerated Dose | *Neoplasm Recurrence, Local/dt [Drug Therapy] | Neoplasm Recurrence, Local/mo [Mortality] | Pyrroles/ad [Administration & Dosage] | Pyrroles/ae [Adverse Effects] | Pyrroles/pk [Pharmacokinetics] | Taxoids/ad [Administration & Dosage] | Taxoids/ae [Adverse Effects] | Taxoids/pk [Pharmacokinetics]Institution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Clinical Trial, Phase I | Clinical Trial, Phase II | Journal Article | Research Support, Non-U.S. Gov'tOnline resources: Click here to access online Digital Object Identifier: http://dx.doi.org/10.1097/JTO.0000000000000027 (Click here) Abbreviated citation: J Thorac Oncol. 9(1):121-5, 2014 Jan.Local Holdings: Available online through MWHC library: 2006 - present.Abstract: INTRODUCTION: The proapoptotic small-molecule pan-Bcl-2 inhibitor obatoclax mesylate (GX15-070) may enhance the cytotoxicity of chemotherapy in relapsed/refractory non-small-cell lung cancer (NSCLC).Abstract: METHODS: Obatoclax was administered with docetaxel in patients with relapsed or refractory NSCLC- docetaxel as a 1-hour infusion on day 1 and obatoclax as a 24-hour infusion on days 1 and 2-every 3 weeks for up to eight cycles. Four dose levels were evaluated in phase 1 (level 1: docetaxel 55 mg/m x 1 and obatoclax 30 mg x 2; levels 2-4: docetaxel 75 mg/m and obatoclax 30 mg, 45 mg, or 60 mg x 2) to identify dose-limiting toxicity and a phase 2 dose. In phase 2, response and tolerability were evaluated.Abstract: RESULTS: Eighteen patients were included in phase 1. Two dose-limiting toxicities occurred during cycle 1: one febrile neutropenia each at dose levels 3 and 4. Maximum tolerated dose was not reached; 32 patients (including 3 from phase 1) were treated in phase 2 with docetaxel 75 mg/m and obatoclax 60 mg (median 2 cycles). Three patients (11%) had partial responses in phase 2; two demonstrated stable disease lasting 12 weeks or more. Median duration of response was 4.8 months. Overall, median progression-free survival was 1.4 months. Neutropenia (31%), febrile neutropenia (16%), and dyspnea (19%) were the most common grade 3/4 adverse events observed.Abstract: CONCLUSIONS: Combined obatoclax mesylate plus docetaxel is tolerable in patients with NSCLC, but response was minimal and neutropenia was a common adverse event.