Panobinostat activity in both bexarotene-exposed and -na?ve patients with refractory cutaneous T-cell lymphoma: Results of a phase II trial

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• 作者：Madeleine Duvic^a ; ^{mduvic@mdanderson.org} ; Reinhard Dummer^b ; Jü ; rgen C. Becker^c ; Nicolas Poulalhon^d ; Pablo Ortiz Romero^e ; Maria Grazia Bernengo^f ; Celeste Lebbé ; ^g ; Chalid Assaf^h ; ⁱ ; Margaret Squier^j ; Denise Williams^j ; Miriam Marshood^j ; Feng Tai^j ; H. Miles Prince^k
• 关键词：Cutaneous T-cell lymphoma ; Panobinostat ; Pan-deacetylase inhibitor ; Mycosis fungoides ; Sé ; zary syndrome ; Bexarotene
• 刊名：European Journal of Cancer
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：49
• 期：2
• 页码：386-394
• 全文大小：283 K

文摘

Background

Panobinostat is a potent, oral pan-deacetylase inhibitor (pan-DACi) that increases the acetylation of proteins involved in multiple oncogenic pathways. Here, panobinostat is studied in bexarotene-exposed and -na?ve patients with refractory cutaneous T-cell lymphoma (CTCL).

Patients and methods

Patients with CTCL subtypes mycosis fungoides and S¨¦zary syndrome who received ?2 prior systemic therapy regimens received panobinostat (20 mg) three times every week. The primary objective was overall response rate (ORR) as determined by a combined evaluation of skin disease and involvement of lymph node and viscera. Disease progression was defined as an unconfirmed, ?25 % increase in modified Severity Weighted Assessment Tool (mSWAT) compared with nadir.

Results

Seventy-nine bexarotene-exposed and 60 bexarotene-na?ve patients were enrolled. Reductions in baseline mSWAT scores were observed in 103 patients (74.1 % ). The ORR was 17.3 % in all patients in the primary analysis (15.2 % and 20.0 % in the bexarotene-exposed and -na?ve groups, respectively). The median progression-free survival was 4.2 and 3.7 months in the bexarotene-exposed and -na?ve groups, respectively. The median duration of response was 5.6 months in the bexarotene-exposed patients and was not reached at data cutoff in the bexarotene-na?ve patients. Additional responses were observed when less-stringent progression criteria were used. The most common adverse events were thrombocytopenia, diarrhoea, fatigue and nausea. Thrombocytopenia and neutropenia were the only grade 3/4 adverse events in >5 % of patients and were manageable.

Conclusion

Despite a very conservative definition of disease progression, panobinostat demonstrated activity with a manageable safety profile in bexarotene-exposed and -na?ve CTCL patients. ClinicalTrials.gov Identifier: .