Obatoclax in combination with fludarabine and rituximab is well-tolerated and shows promising clinical activity in relapsed chronic lymphocytic leukemia

Autor:	David C. Fisher, Bethany Tesar, Lillian Werner, Arnold S. Freedman, Evgeny Mikler, Christina Thompson, Jennifer R. Brown, Naoko Takebe, Lijian Yu, Donna Neuberg, Hazel Reynolds
Rok vydání:	2015
Předmět:	Oncology Adult Male Cancer Research medicine.medical_specialty Indoles Chronic lymphocytic leukemia Pharmacology Neutropenia Relapsed chronic lymphocytic leukemia chemistry.chemical_compound Recurrence Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Pyrroles Aged Neoplasm Staging Chromosome Aberrations business.industry Hematology Middle Aged medicine.disease Combined Modality Therapy Leukemia Lymphocytic Chronic B-Cell Fludarabine Prior Therapy Treatment Outcome chemistry Toxicity Mutation Retreatment Disease Progression Rituximab Female business Biomarkers Vidarabine Obatoclax medicine.drug
Zdroj:	Leukemialymphoma. 56(12)
ISSN:	1029-2403
Popis:	Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins. This phase 1 study combining obatoclax with FR was undertaken in chronic lymphocytic leukemia (CLL) patients relapsed after at least one prior therapy. Obatoclax was given as a 3-h infusion on days 1 and 3 and escalated through three dose levels, with standard dose FR days 1-5. Thirteen patients were enrolled, with a median of two prior therapies. One dose-limiting toxicity (DLT) of a 2-week treatment delay for persistent grade 2-3 neutropenia was observed at the highest obatoclax dose (20 mg/m2), but no maximum tolerated dose (MTD) was reached. The overall response rate (ORR) was 85%, with 15% complete responses (CRs) by NCI-96 criteria and 54% by IWCLL 2008 criteria. Median time to progression was 20 months. It is concluded that obatoclax can be safely administered to relapsed CLL patients in combination with FR and shows promising clinical activity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1a63336315b62273231118e2e2921823 https://pubmed.ncbi.nlm.nih.gov/25971907 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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