Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

• Published in: Journal of clinical oncology Vol. 29; no. 9; pp. 1198 - 1203
• Main Authors: KIRSCHBAUM, Mark, FRANKEL, Paul, NADEMANEE, Auayporn, FORMAN, Stephen J, GANDARA, David, NEWMAN, Edward, POPPLEWELL, Leslie, ZAIN, Jasmine, DELIOUKINA, Maria, PULLARKAT, Vinod, MATSUOKA, Deron, PULONE, Bernadette, ROTTER, Arnold J, ESPINOZA-DELGADO, Igor
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.03.2011
• Subjects: Administration, Oral; Adult; Aged; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Drug Resistance, Neoplasm - drug effects; Female; Hematologic and hematopoietic diseases; Humans; Hydroxamic Acids - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell, Marginal Zone - drug therapy; Lymphoma, B-Cell, Marginal Zone - pathology; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - pathology; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - pathology; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Original Reports; Remission Induction; Salvage Therapy; Survival Rate; Treatment Outcome; Tumors; Antineoplastic agent; Relapse; Treatment resistance; B cell neoplasm; Malignant hemopathy; B-Lymphocyte; Non Hodgkin lymphoma; Histone deacetylase inhibitor; Cancerology; Treatment; Lymphoproliferative syndrome; Vorinostat; Phase II trial; Mantle cell lymphoma; Indolent lymphoma; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.32.1398

We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.