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Long‐term efficacy and safety of bexarotene for Japanese patients with cutaneous T‐cell lymphoma: The results of a phase 2 study (B‐1201)
Author(s) -
Hamada Toshihisa,
Tokura Yoshiki,
Sugaya Makoto,
Ohtsuka Mikio,
Tsuboi Ryoji,
Nagatani Tetsuo,
Kiyohara Eiji,
Tani Mamori,
Setoyama Mitsuru,
Matsushita Shigeto,
Kawai Kazuhiro,
Yonekura Kentaro,
Saida Toshiaki,
Iwatsuki Keiji
Publication year - 2019
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.14923
Subject(s) - medicine , bexarotene , tolerability , neutropenia , discontinuation , leukopenia , adverse effect , population , gastroenterology , surgery , toxicity , biochemistry , chemistry , environmental health , nuclear receptor , transcription factor , gene
The present study (B‐1201 clinical trial) was conducted as a multicenter, open‐label, single‐arm phase II study to evaluate the long‐term safety, tolerability and efficacy of bexarotene. This study enrolled 10 Japanese adults aged more than 20 years with cutaneous T‐cell lymphoma ( CTCL ) who completed the 24‐week study period of the B‐1101 trial. The objective response rate (ORR) was 53.8% (95% confidence interval, 25.1–80.8). In the early stage ( IB ), the ORR was 60% (3/5 cases). In the advanced stage ( IIB and IIIA ), the ORR was 57.1% (4/7 cases). The median time to response was 58 days (range, 27–168). The median treatment duration was 380 days (range, 33–1674). The median duration of response ( DOR ) could not be reached during the study period. The longest DOR reached 1618 days at the end of the B‐1201 trial. Nine patients (56.3%) in the full analysis set ( FAS ) population experienced dose reduction of bexarotene. Common drug‐related adverse events in the FAS population included hypothyroidism (93.8%), hypertriglyceridemia (81.3%), hypercholesterolemia (81.3%), leukopenia (68.8%) and neutropenia (56.3%). Dose‐limiting toxicity ( DLT ) was present in five (38.5%) of the 13 patients in the 300 mg/m 2 cohort. Of the five patients, four developed grade 3 neutropenia and one developed grade 4 hypertriglyceridemia. All DLT cases recovered after the discontinuation of bexarotene. None of the five patients discontinued this trial because of DLT . The B‐1201 trial shows the long‐term safety of oral bexarotene for Japanese patients with CTCL , despite frequent dose reduction.