{'fraction_non_alphanumeric': 0.04218880534670008, 'fraction_numerical': 0.03467000835421888, 'mean_word_length': 4.9875, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Safety, tolerability, and PK of topical calcitriol formulation for treatment of chemotherapy-induced alopecia (CIA) in patients receiving taxane-based regimen: Final results.

11608 Background: Chemotherapy-induced alopecia (CIA) following taxane-based treatment regimen is due to direct toxicity of these agents on rapidly dividing cells within hair follicles. Currently no oral or topical agents have been approved for prevention of CIA. In murine studies, topical calcitriol reduced CIA, likely due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy. Methods: A 3+3 dose-escalation strategy was used in this Phase 1 study with 3-6 patients at six dose levels (5/10/20/40/60/80 μg/mL) were assessed for safety and tolerability of BPM31543. Patients with a diagnosis of breast cancer, gynecologic cancer or sarcomas receiving a taxane-based chemotherapy regimen applied 1mL of the formulation to the scalp BID, ≥ 5 days prior to starting chemotherapy for at least 3 months or until treatment completed. Safety and efficacy assessments included AE monitoring, PK analysis, blinded photographic assessments and patient self-assessment. Results: 22/23 (95.7%) female patients receiving treatment and included in the safety population experienced at least one TEAE. The most frequently experienced TEAEs were alopecia (14 pts; 60.9%), fatigue (11 pts; 47.8%), nausea (9 pts; 39.1%), peripheral sensory neuropathy (7 pts; 30.4%), and maculopapular rash and vitamin D increased each in six patients (26.1%). Of these, elevated vitamin D and rash were possibly or probably related to treatment. Fatigue, nausea, and neuropathy were likely due to chemotherapy. In 18 patients included in the post-dose versus pre-treatment comparison, there was no dose-dependency on systemic levels of calcitriol. Hair loss < 50% from baseline was observed in 8 patients at week 7 that was maintained at week 15 in 2 patients. Conclusions: Study results showed BPM31543 applied topically twice daily to the scalp in patients receiving taxane-based chemotherapy was safe and well-tolerated. No DLT was observed up to 80 µg/mL dose and no MTD level was reached. There was a signal of potential efficacy detected at each dose level. A seamless Phase 2/3 trial strategy for clinical development is planned. Clinical trial information: NCT01588522.