A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia.

Autor: Lacouture ME; Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 East 74th Street, New York, NY, 10021, USA. lacoutum@mskcc.org., Dion H; BERG LLC, Framingham, MA, USA., Ravipaty S; BERG LLC, Framingham, MA, USA., Jimenez JJ; Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA., Thapa K; BERG LLC, Framingham, MA, USA., Grund EM; BERG LLC, Framingham, MA, USA., Benaim E; BERG LLC, Framingham, MA, USA., Tanna N; BERG LLC, Framingham, MA, USA., Luan S; BERG LLC, Framingham, MA, USA., DiTommaso N; BERG LLC, Framingham, MA, USA., Narain NR; BERG LLC, Framingham, MA, USA., Sarangarajan R; BERG LLC, Framingham, MA, USA., Granger E; BERG LLC, Framingham, MA, USA., Berman B; Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA., Goldfarb SB; Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 East 74th Street, New York, NY, 10021, USA. lacoutum@mskcc.org.; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA. lacoutum@mskcc.org.; Breast Medicine Service Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA. lacoutum@mskcc.org.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2021 Feb; Vol. 186 (1), pp. 107-114. Date of Electronic Publication: 2020 Nov 18.
DOI: 10.1007/s10549-020-06005-6
Abstrakt: Purpose: Chemotherapy-induced alopecia (CIA) negatively affects psychosocial health and quality of life (QoL). Currently, there are no approved pharmacologic agents to prevent CIA. Here, we evaluated the safety, tolerability, and potential signal of efficacy of topical calcitriol (BPM31543) on CIA prevention.
Materials and Methods: This Phase 1 trial included 23 female patients with breast cancer, gynecologic cancer, or sarcomas receiving a taxane-based chemotherapy. Patients received a 3 + 3 dose-escalation regimen at 5, 10, 20, 40, 60, and 80 μg/mL, with 3-6 patients per group. Patients applied topical BPM31543 to the scalp twice a day for 2 weeks prior to chemotherapy and continued until chemotherapy treatment was completed. The maximum tolerated dose (MTD) during first 28 day application was determined. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments, and patient self-assessment were evaluated.
Results: Out of 23 patients treated with BPM31543, 8 patients experienced at least 1 treatment-related adverse event (AE). The majority of AEs were mild to moderate in severity. Only 1 patient experienced SAEs (vomiting, nausea, fever, and flank pain) considered treatment related. Alopecia < 50% from baseline was observed in 8 patients at Week 7, and, of which 2 patients had < 50% alopecia maintained at Week 15. There were no detectable effects of topical BPM31543 on serum levels of calcitriol.
Conclusions: BPM31543 applied topically twice daily to the scalp is safe and well tolerated in patients receiving taxane-based chemotherapy. No DLT was observed at up to 80 µg/mL, and MTD was not reached. Based on the data from this trial, BPM31543 represents a promising therapy and warrants further investigation in Phase 2/3 trials.
Databáze: MEDLINE
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