Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas
| Autor: | Toshiaki Saida, Keiji Iwatsuki, Kentaro Yonekura, Kazuhiro Kawai, Toshihisa Hamada, Ryoji Tsuboi, Tetsuo Nagatani, Tsuyoshi Yoshida, Makoto Sugaya, Shigeto Matsushita, Mamori Tani, Yoshiki Tokura, Mikio Ohtsuka, Mitsuru Setoyama |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Tetrahydronaphthalenes Dermatology Neutropenia Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Anticarcinogenic Agents Humans Medicine Adverse effect Aged Bexarotene Leukopenia business.industry Hypertriglyceridemia Cutaneous T-cell lymphoma General Medicine Middle Aged medicine.disease Lymphoma T-Cell Cutaneous Retinoid X Receptors Treatment Outcome 030104 developmental biology Endocrinology Tolerability 030220 oncology & carcinogenesis Female medicine.symptom business medicine.drug |
| Zdroj: | The Journal of Dermatology. 44:135-142 |
| ISSN: | 0385-2407 |
| DOI: | 10.1111/1346-8138.13542 |
| Popis: | Safety, tolerability, pharmacokinetics and efficacy of bexarotene, a novel retinoid X receptor (RXR)-selective retinoid, were evaluated in Japanese patients with stage IIB-IVB and relapsed/refractory stage IB-IIA cutaneous T-cell lymphomas (CTCL). This study was conducted as a multicenter, open-label, historically controlled, single-arm phase I/II study. Bexarotene was p.o. administrated once daily at a dose of 300 mg/m2 for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m2 in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m2 met the response criteria using the modified severity-weighted assessment tool (mSWAT) at 24 weeks or discontinuation. Dose-limiting toxic effects (DLT) were present in four of 13 patients (31%) at a dose of 300 mg/m2 : two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m2 bexarotene. In the 13 patients at 300 mg/m2 , common drug-related adverse events (AE) included hypothyroidism (92%), hypercholesterolemia (77%), leukopenia or neutropenia (39%), nasopharyngitis or anemia (31%). The treatment-related grade 3 AE included hypertriglyceridemia (4/16 patients, 25%), increased alanine aminotransferase, increased aspartate aminotransferase, dyslipidaemia, leukopenia and neutropenia (1/16 patients, 6%), and one of 16 patients experienced grade 4 hypertriglyceridemia. No patients discontinued bexarotene due to the AE during the study, but dose reduction or suspension was required. Bexarotene was shown to be well tolerated at 300 mg/m2 once daily and effective in Japanese patients with CTCL. |
| Databáze: | OpenAIRE |
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