Phase I studies of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma: a pooled analysis of two phase I studies conducted in Japan and Korea.

Abstract

OBJECTIVE:

Two phase I studies of darinaparsin including Japanese and Korean patients with relapsed/refractory peripheral T-cell lymphoma were performed to evaluate its safety (primary purpose), efficacy and pharmacokinetic profile (ClinicalTrials.gov: NCT01435863 and NCT01689220).

METHODS:

Patients received intravenous darinaparsin for 5 consecutive days at 200 mg/m2/day in 4-week cycles, 300 mg/m2/day in 4-week cycles or 300 mg/m2/day in 3-week cycles.

RESULTS:

Seventeen Japanese and 6 Korean patients were enrolled and treated. Drug-related adverse events developed in 18 patients (78%). Dose-limiting toxicity, grade 3 hepatic dysfunction, was reported on Day 15 of cycle 1 in 1 Japanese patient who received 300 mg/m2/day. The most common drug-related, grade ≥ 3 adverse events were lymphopenia (9%), neutropenia (9%) and thrombocytopenia (9%). No deaths occurred. In 14 evaluable patients, 1 and 3 patients had complete response and partial response, respectively. The plasma concentration-time profiles of arsenic, a surrogate marker for darinaparsin, were similar between Japanese and Korean patients. No significant difference was found in its pharmacokinetic profile.

CONCLUSIONS:

These data indicate the good tolerability and potential efficacy of darinaparsin in patients with relapsed/refractory peripheral T-cell lymphoma. Darinaparsin 300 mg/m2/day for 5 consecutive days in 3-week cycles is the recommended regimen for phase II study.

• Authors: Michinori Ogura, Won-Seog Kim, Toshiki Uchida, Naokuni Uike, Youko Suehiro, Kenichi Ishizawa, Hirokazu Nagai, Fumiko Nagahama, Yusuke Sonehara, Kensei Tobinai
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 51 Issue 2 Pg. 218-227 (Feb 08 2021) ISSN: 1465-3621 [Electronic] England
• PMID: 33051668 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
• Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Arsenicals
• darinaparsin
• Glutathione

Topics

• Adult
• Aged
• Aged, 80 and over
• Arsenicals (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Female
• Glutathione (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Humans
• Japan
• Lymphoma, T-Cell, Peripheral (drug therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Republic of Korea
• Time Factors
• Treatment Outcome
• Young Adult