医学
紫杉烷
前列腺癌
中性粒细胞减少症
不利影响
内科学
卡巴齐塔塞尔
雄激素剥夺疗法
肿瘤科
癌症
化疗
耐受性
加药
转移性乳腺癌
泌尿科
乳腺癌
作者
Mark C. Markowski,Ronald F. Tutrone,Christopher Michael Pieczonka,K. Gary Barnette,Robert H. Getzenberg,Domingo Rodriguez,Mitchell S. Steiner,Daniel Saltzstein,Mario A. Eisenberger,Emmanuel S. Antonarakis
标识
DOI:10.1158/1078-0432.ccr-22-0162
摘要
Abstract Purpose: Sabizabulin, an oral cytoskeleton disruptor, was tested in a phase Ib/II clinical study in men with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods: The phase Ib portion utilized a 3+3 design with escalating daily oral doses of 4.5–81 mg and increasing schedule in 39 patients with mCRPC treated with one or more androgen receptor–targeting agents. Prior taxane chemotherapy was allowed. The phase II portion tested a daily dose of 63 mg in 41 patients with no prior chemotherapy. Efficacy was assessed using PCWG3 and RECIST 1.1 criteria. Results: The MTD was not defined in the phase Ib and the recommended phase II dose was set at 63 mg/day. The most common adverse events (>10% frequency) at the 63 mg oral daily dosing (combined phase Ib/II data) were predominantly grade 1–2 events. Grade ≥3 events included diarrhea (7.4%), fatigue (5.6%), and alanine aminotransferase/aspartate aminotransferase elevations (5.6% and 3.7%, respectively). Neurotoxicity and neutropenia were not observed. Preliminary efficacy data in patients treated with ≥1 continuous cycle of 63 mg or higher included objective response rate in 6 of 29 (20.7%) patients with measurable disease (1 complete, 5 partial) and 14 of 48 (29.2%) patients had PSA declines. The Kaplan–Meier median radiographic progression-free survival was estimated to be 11.4 months (n = 55). Durable responses lasting >2.75 years were observed. Conclusions: This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with preliminary antitumor activity. These data support the ongoing phase III VERACITY trial of sabizabulin in men with mCRPC.
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