TY - JOUR
T1 - Phase-I and randomized phase-II trial of panobinostat in combination with ICE (Ifosfamide, carboplatin, etoposide) in relapsed or refractory classical hodgkin lymphoma
AU - Hu, Bei
AU - Younes, Anas
AU - Westin, Jason R.
AU - Turturro, Francesco
AU - Claret, Linda
AU - Feng, Lei
AU - Fowler, Nathan
AU - Neelapu, Sattva
AU - Romaguera, Jorge
AU - Hagemeister, Fredrick B.
AU - Rodriguez, Maria Alma
AU - Samaniego, Felipe
AU - Fayad, Luis E.
AU - Copeland, Amanda R.
AU - Nastoupil, Loretta J.
AU - Nieto, Yago
AU - Fanale, Michelle A.
AU - Oki, Yasuhiro
N1 - Publisher Copyright:
© 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/8/10
Y1 - 2018/8/10
N2 - 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 30mg (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.
AB - 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 30mg (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.
KW - Classical Hodgkin lymphoma
KW - Histone deacetylase inhibitors
KW - Panobinostat
KW - Phase-I study
KW - Phase-II study
KW - Salvage chemotherapy
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U2 - 10.1080/10428194.2017.1359741
DO - 10.1080/10428194.2017.1359741
M3 - Article
C2 - 28792260
AN - SCOPUS:85027176123
SN - 1042-8194
VL - 59
SP - 863
EP - 870
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 4
ER -