Abstract
This phase-I/phase-II study evaluated panobinostat in combination with ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory classical Hodgkin lymphoma. During phase I, panobinostat was given daily on Monday/Wednesday/Friday starting one week prior to Cycle 1 (C1) of ICE and during two weeks of C1-2 of ICE (Schedule A). No DLT was observed at 30 mg. However, frequent (84%) grade-4 thrombocytopenia during second week prompted us to omit the second week of panobinostat 30 mg (Schedule B) for phase II, where this regimen was compared to ICE. In the randomized phase-II study, CR was seen in 9/11 (82%) and 8/12 (67%) for P-ICE and ICE, respectively (p = .64). Grade-4 neutropenia (55% vs. 8%) and thrombocytopenia (100% vs. 33%) were more common in P-ICE. In summary, combination therapy using panobinostat produced high CR rate at the cost of greater bone marrow toxicity. Investigation of panobinostat with less myelosuppressive agents is of interest.
Keywords:
Classical Hodgkin lymphoma; histone deacetylase inhibitors; panobinostat; phase-I study; phase-II study; salvage chemotherapy.
Publication types
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Clinical Trial, Phase I
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Clinical Trial, Phase II
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Comparative Study
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Randomized Controlled Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Bone Marrow / drug effects
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Carboplatin / therapeutic use
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Drug Administration Schedule
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Drug Resistance, Neoplasm
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Etoposide / therapeutic use
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Female
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Histone Deacetylase Inhibitors / administration & dosage
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Histone Deacetylase Inhibitors / adverse effects
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Histone Deacetylase Inhibitors / therapeutic use*
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Hodgkin Disease / drug therapy*
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Hodgkin Disease / mortality
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Hodgkin Disease / pathology
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Humans
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Ifosfamide / therapeutic use
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Male
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Middle Aged
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Neoplasm Recurrence, Local / drug therapy*
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Neoplasm Recurrence, Local / pathology
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Neutropenia / chemically induced
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Neutropenia / epidemiology
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Panobinostat / administration & dosage
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Panobinostat / adverse effects
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Panobinostat / therapeutic use*
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Survival Rate
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Thrombocytopenia / chemically induced
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Thrombocytopenia / epidemiology
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Treatment Outcome
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Young Adult
Substances
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Histone Deacetylase Inhibitors
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Etoposide
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Panobinostat
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Carboplatin
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Ifosfamide