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Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lympho...

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Autores principales: Tang, Tiffany, Martin, Peter, Somasundaram, Nagavalli, Lim, Cindy, Tao, Miriam, Poon, Eileen, Yunon, Maica J.D., Toh, Shu Q., Yan, Sean X., Farid, Mohamad, Chan, Jason Y., Lim, Soon T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634181/
https://www.ncbi.nlm.nih.gov/pubmed/33147935
http://dx.doi.org/10.3324/haematol.2020.251454
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author Tang, Tiffany
Martin, Peter
Somasundaram, Nagavalli
Lim, Cindy
Tao, Miriam
Poon, Eileen
Yunon, Maica J.D.
Toh, Shu Q.
Yan, Sean X.
Farid, Mohamad
Chan, Jason Y.
Lim, Soon T.
author_facet Tang, Tiffany
Martin, Peter
Somasundaram, Nagavalli
Lim, Cindy
Tao, Miriam
Poon, Eileen
Yunon, Maica J.D.
Toh, Shu Q.
Yan, Sean X.
Farid, Mohamad
Chan, Jason Y.
Lim, Soon T.
author_sort Tang, Tiffany
collection PubMed
description Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerated dose of selinexor was 40 mg when combined with DICE. The combination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltrials. gov identifier: NCT03212937).
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spelling pubmed-86341812021-12-17 Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma Tang, Tiffany Martin, Peter Somasundaram, Nagavalli Lim, Cindy Tao, Miriam Poon, Eileen Yunon, Maica J.D. Toh, Shu Q. Yan, Sean X. Farid, Mohamad Chan, Jason Y. Lim, Soon T. Haematologica Article Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerated dose of selinexor was 40 mg when combined with DICE. The combination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltrials. gov identifier: NCT03212937). Fondazione Ferrata Storti 2020-11-05 /pmc/articles/PMC8634181/ /pubmed/33147935 http://dx.doi.org/10.3324/haematol.2020.251454 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Tang, Tiffany
Martin, Peter
Somasundaram, Nagavalli
Lim, Cindy
Tao, Miriam
Poon, Eileen
Yunon, Maica J.D.
Toh, Shu Q.
Yan, Sean X.
Farid, Mohamad
Chan, Jason Y.
Lim, Soon T.
Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
title Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
title_full Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
title_fullStr Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
title_full_unstemmed Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
title_short Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
title_sort phase i study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral t-cell or natural-killer/t-cell lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634181/
https://www.ncbi.nlm.nih.gov/pubmed/33147935
http://dx.doi.org/10.3324/haematol.2020.251454
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