Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 3063
© 2006 American Society of Clinical Oncology

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Abstract

International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report

St. Thomas’ Hospital, London, United Kingdom; Gloucester Pharmaceuticals, Inc., Cambridge, MA; Medical University, Lodz, Poland; Medical University, Wroclaw, Poland; Royal Free Hospital, London, United Kingdom

3063

Background: Depsipeptide, a unique bicyclic peptide histone deacetylase inhibitor (HDACi), has shown activity in a range of in vitro and in vivo tumor models and clinical activity in T-cell lymphomas and prostate cancer. This study seeks to confirm the CTCL activity previously reported by the NCI (Piekarz, et al., ASCO, 2004). Methods: Single-arm, open label study, in 25 centers in the UK, Germany, Poland and the US. Patients aged 18 years with biopsy-confirmed CTCL (centrally reviewed) who have failed at least one prior systemic treatment receive up to 6 cycles of depsipeptide as a 4-hour IV infusion on Days 1, 8 and 15 q 28 days. Eligibility criteria include: mycosis fungoides and Sézary syndrome plus variants, Stages IB - IVA, adequate organ function, ECOG PS 1. Patients with significant cardiovascular abnormalities are excluded in addition to those taking QTc-prolonging or CYP3A4-inhibiting drugs. The primary endpoint is overall reponse rate measured by a combination of imaging, circulating cell counts and a weighted skin average instrument, confirmed by standardized photography. A subset undergoes pharmacokinetic assessments. Correlative studies include acetylation status, apoptotic markers and proteomic analyses where possible. Target accrual is 76 to yield 64 evaluable patients. Results: 30 patients have received treatment with 17 evaluable for efficacy. Responses seen are 1 cCR, 4 PRs (duration 2+ to 6 months) 9 SD and 3 PD. 3 patients withdrew early for PD and 2 for other reasons. The remaining patients on study are too early to assess. Most frequent toxicities are: nausea/vomiting, fatigue, myelosuppression and asymptomatic ECG changes. No patient has withdrawn for toxicity and there have been no treatment-related deaths. Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gloucester Pharmaceuticals Gloucester Pharmaceuticals Gloucester Pharmaceuticals

Abstract presentation from the 2006 ASCO Annual Meeting