Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma.

Abstract

Pralatrexate is a novel antifolate approved in the USA for the treatment of relapsed or refractory peripheral T-cell lymphoma. To assess its safety, efficacy, and pharmacokinetics in Japanese patients with this disease, we undertook a phase I/II study. Pralatrexate was given i.v. weekly for 6 weeks of a 7-week cycle. All patients received concurrent vitamin B12 and folic acid. In phase I, three patients received pralatrexate 30 mg/m2 and none experienced a dose-limiting toxicity. In phase II, we treated 22 additional patients with that dose. The median number of treatment cycles was 1 (range, 1-9). Nine of 20 evaluable patients (45%) achieved an objective response by central review, including two complete responses. All responses occurred within the first treatment cycle. At the time of data cut-off, median progression-free survival was 150 days. Median overall survival was not reached. In the total population, the most commonly reported adverse events included mucositis (88%), thrombocytopenia (68%), liver function test abnormality (64%), anemia (60%), and lymphopenia (56%). Grade 3/4 adverse events included lymphopenia (52%), thrombocytopenia (40%), leukopenia (28%), neutropenia (24%), anemia (20%), and mucositis (20%). The pharmacokinetic profile showed no drug accumulation with repeat dosing. These results indicate that pralatrexate is generally well tolerated and effective in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. This trial was registered with ClinicalTrials.gov (NCT02013362).

• Authors: Dai Maruyama, Hirokazu Nagai, Yoshinobu Maeda, Takahiko Nakane, Tatsu Shimoyama, Tomonori Nakazato, Rika Sakai, Takayuki Ishikawa, Koji Izutsu, Ryuzo Ueda, Kensei Tobinai
• Journal: Cancer science (Cancer Sci) Vol. 108 Issue 10 Pg. 2061-2068 (Oct 2017) ISSN: 1349-7006 [Electronic] England
• PMID: 28771889 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• 10-propargyl-10-deazaaminopterin
• Folic Acid
• Aminopterin
• Vitamin B 12

Topics

• Adult
• Aged
• Aged, 80 and over
• Aminopterin (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Drug Administration Schedule
• Female
• Folic Acid (administration & dosage, therapeutic use)
• Humans
• Japan
• Lymphoma, T-Cell, Peripheral (drug therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Survival Analysis
• Treatment Outcome
• Vitamin B 12 (administration & dosage, therapeutic use)