Department of Medicine, Section of Hematology/Oncology, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA; Department of Medicine, Division of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL, USA(1).
Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
Oral Oncol. 2021 Mar;114:105171. doi: 10.1016/j.oraloncology.2020.105171. Epub 2021 Jan 26.
We report the results of this phase I study to evaluate the maximum tolerated dose (MTD) and safety of veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin and paclitaxel induction chemotherapy (IC) for locoregionally advanced head and neck squamous cell carcinoma (HNSCC).
In a 3 + 3 cohort design, patients with stage IVA-B human papillomavirus-negative HNSCC received 2 cycles of carboplatin (AUC 6, day 1), paclitaxel (100 mg/m, days 1, 8, 15) and veliparib (days 1-7) every 21 days followed by standard curative-intent chemoradiotherapy. Primary endpoint: MTD and recommended phase II dose (RP2D) as determined by the first IC cycle.
Twenty patients enrolled. Two withdrew before treatment; 18 patients were analyzed. Median age was 63 years. Primary disease sites included hypopharynx (n = 5), larynx (n = 5), oral cavity (n = 4), oropharynx (n = 3), and nasal cavity (n = 1). Through all of IC, the most common grade 3 + adverse events (AEs) were neutropenia (33%), thrombocytopenia (33%), anemia (11%), and white blood cell decrease (11%). One patient experienced a hematologic DLT at 350 mg BID. The RP2D for veliparib combined with carboplatin/paclitaxel is 350 mg BID. With 40.9 month median follow-up across dose levels for all patients, the 24-month overall and progression free survival was 77.8% (95% CI 60.8-99.6%) and 66.7% (95% CI 48.1-92.4%), respectively. Medians have not been reached.
Addition of veliparib to carboplatin and paclitaxel IC was well tolerated in patients with advanced HNSCC. Hematologic toxicities were the most common AEs.
我们报告了这项 I 期研究的结果，该研究评估了多聚（ADP-核糖）聚合酶（PARP）抑制剂维利帕尼（veliparib）联合卡铂和紫杉醇诱导化疗（IC）治疗局部晚期头颈部鳞状细胞癌（HNSCC）的最大耐受剂量（MTD）和安全性。
采用 3+3 队列设计，人乳头瘤病毒阴性 IVA-B 期 HNSCC 患者接受 2 个周期的卡铂（AUC 6，第 1 天）、紫杉醇（100mg/m，第 1、8、15 天）和维利帕尼（第 1-7 天），每 21 天一次，随后进行标准的根治性放化疗。主要终点：由第 1 个 IC 周期确定的 MTD 和推荐的 II 期剂量（RP2D）。
共纳入 20 例患者。2 例在治疗前退出，18 例患者进行了分析。中位年龄为 63 岁。主要疾病部位包括下咽（n=5）、喉（n=5）、口腔（n=4）、口咽（n=3）和鼻腔（n=1）。整个 IC 期间，最常见的 3+级不良事件（AE）为中性粒细胞减少症（33%）、血小板减少症（33%）、贫血（11%）和白细胞减少症（11%）。1 例患者在 350mg BID 时出现血液学 DLT。维利帕尼联合卡铂/紫杉醇的 RP2D 为 350mg BID。在所有剂量水平的患者中，中位随访时间为 40.9 个月，24 个月的总生存率和无进展生存率分别为 77.8%（95%CI 60.8-99.6%）和 66.7%（95%CI 48.1-92.4%），中位生存期尚未达到。
维利帕尼联合卡铂和紫杉醇 IC 治疗晚期 HNSCC 患者耐受性良好。血液学毒性是最常见的 AE。
