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E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study

E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin‐2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase I study was carried out to evalua...

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Autores principales: Ohmachi, Ken, Ando, Kiyoshi, Ogura, Michinori, Uchida, Toshiki, Tobinai, Kensei, Maruyama, Dai, Namiki, Masayuki, Nakanishi, Tadashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834772/
https://www.ncbi.nlm.nih.gov/pubmed/29363235
http://dx.doi.org/10.1111/cas.13513
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author Ohmachi, Ken
Ando, Kiyoshi
Ogura, Michinori
Uchida, Toshiki
Tobinai, Kensei
Maruyama, Dai
Namiki, Masayuki
Nakanishi, Tadashi
author_facet Ohmachi, Ken
Ando, Kiyoshi
Ogura, Michinori
Uchida, Toshiki
Tobinai, Kensei
Maruyama, Dai
Namiki, Masayuki
Nakanishi, Tadashi
author_sort Ohmachi, Ken
collection PubMed
description E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin‐2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase I study was carried out to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma. E7777 (6, 12, and expanded 9 μg/kg/day) was given to 13 patients by i.v. infusion on five consecutive days per 21‐day cycle. Dose‐limiting toxicities, including increased alanine aminotransferase, hyponatremia (n = 2), hypokalemia, lymphopenia, fatigue, hypoalbuminemia, rash, and increased lipase (n = 1), were observed in all three patients in the 12 μg/kg/day cohort, whereas two of six patients in the 9 μg/kg/day cohort showed decreased appetite or fatigue. The maximum tolerated and recommended dose of E7777 was 9 μg/kg/day for five consecutive days per 21‐day cycle. The objective response rate was 38% (5/13) and did not appear to depend on tumor expression of CD25. E7777 was well tolerated, assuming careful management of adverse events during treatment, and preliminary but clinically meaningful antitumor activity was observed. Subsequent studies of E7777 for T‐cell lymphomas are warranted. This study was registered with www.ClinicalTrials.gov (NCT1401530).
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spelling pubmed-58347722018-03-06 E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study Ohmachi, Ken Ando, Kiyoshi Ogura, Michinori Uchida, Toshiki Tobinai, Kensei Maruyama, Dai Namiki, Masayuki Nakanishi, Tadashi Cancer Sci Original Articles E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin‐2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase I study was carried out to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma. E7777 (6, 12, and expanded 9 μg/kg/day) was given to 13 patients by i.v. infusion on five consecutive days per 21‐day cycle. Dose‐limiting toxicities, including increased alanine aminotransferase, hyponatremia (n = 2), hypokalemia, lymphopenia, fatigue, hypoalbuminemia, rash, and increased lipase (n = 1), were observed in all three patients in the 12 μg/kg/day cohort, whereas two of six patients in the 9 μg/kg/day cohort showed decreased appetite or fatigue. The maximum tolerated and recommended dose of E7777 was 9 μg/kg/day for five consecutive days per 21‐day cycle. The objective response rate was 38% (5/13) and did not appear to depend on tumor expression of CD25. E7777 was well tolerated, assuming careful management of adverse events during treatment, and preliminary but clinically meaningful antitumor activity was observed. Subsequent studies of E7777 for T‐cell lymphomas are warranted. This study was registered with www.ClinicalTrials.gov (NCT1401530). John Wiley and Sons Inc. 2018-02-26 2018-03 /pmc/articles/PMC5834772/ /pubmed/29363235 http://dx.doi.org/10.1111/cas.13513 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Ohmachi, Ken
Ando, Kiyoshi
Ogura, Michinori
Uchida, Toshiki
Tobinai, Kensei
Maruyama, Dai
Namiki, Masayuki
Nakanishi, Tadashi
E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study
title E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study
title_full E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study
title_fullStr E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study
title_full_unstemmed E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study
title_short E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study
title_sort e7777 in japanese patients with relapsed/refractory peripheral and cutaneous t‐cell lymphoma: a phase i study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834772/
https://www.ncbi.nlm.nih.gov/pubmed/29363235
http://dx.doi.org/10.1111/cas.13513
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