[Pharmacological profile and clinical study results of darinaparsin (DARVIAS® injection 135â
|mg), an organic arsenic product, for relapsed or refractory peripheral t-cell lymphoma].
Nihon Yakurigaku Zasshi
; 158(5): 408-418, 2023.
Article
in Ja
| MEDLINE
| ID: mdl-37673618
ABSTRACT
Darinaparsin, an active ingredient of DARVIAS® Injection 135â
|mg, is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione. Darinaparsin is thought to induce apoptosis and cell-cycle arrest and suppress tumor growth by disrupting mitochondrial functions and increasing production of intracellular reactive oxygen species. Darinaparsin is processed at the cell surface by γ-glutamyltranspeptidase (γ-GT), leading to formation of dimethylarsino-cysteine, which is imported via a cystine transporter expressed on cell surface membranes. Numerous tumor cells express high levels of γ-GT and cystine transporter, to maintain high levels of glutathione as an intracellular antioxidant. Darinaparsin is a novel antineoplastic agent designed to exploit the characteristics of tumor cells and to be efficiently taken up by tumor cells to inhibit their growth. In a global phase 2 pivotal study of darinaparsin in Asian patients with relapsed or refractory peripheral T-cell lymphoma (r/r PTCL), the overall response rate was 19.3% (90% confidence interval 11.2-29.9%) and grade ≥3 drug-related adverse events with an incidence rate ≥5% included neutropenia (9.2%, n = 6), anemia (6.2%, n = 4) and thrombocytopenia (6.2%, n = 4) in 65 patients receiving darinaparsin. Based on the results of this phase 2 trial, which demonstrated the anti-tumor activity and acceptable safety profile of darinaparsin in patients with r/r PTCL, Solasia pharma K.K. received approval for darinaparsin for the treatment of r/r PTCL in June 2022, and Nippon Kayaku Co., Ltd. launched this drug in August 2022. Darinaparsin is expected to contribute to the clinical practice of PTCL as a new treatment option for this disease.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arsenic
/
Arsenicals
/
Lymphoma, T-Cell, Peripheral
Limits:
Humans
Language:
Ja
Journal:
Nihon Yakurigaku Zasshi
Year:
2023
Document type:
Article