Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma.

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Mark Kirschbaum, Paul Frankel, Leslie Popplewell, Jasmine Zain, Maria Delioukina, Vinod Pullarkat, Deron Matsuoka, Bernadette Pulone, Arnold J Rotter, Igor Espinoza-Delgado, Auayporn Nademanee, Stephen J Forman, David Gandara, Edward Newman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 9 Pg. 1198-203 (Mar 20 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21300924 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Hydroxamic Acids
• Vorinostat

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Hydroxamic Acids (therapeutic use)
• Lymphoma, B-Cell, Marginal Zone (drug therapy, pathology)
• Lymphoma, Follicular (drug therapy, pathology)
• Lymphoma, Mantle-Cell (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Remission Induction
• Salvage Therapy
• Survival Rate
• Treatment Outcome
• Vorinostat