A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study.
A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study.
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DOI：
10.1016/j.ygyno.2015.11.024
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发表时间：
2016-02
影响因子：
4.7
通讯作者：
Fracasso PM
中科院分区：
文献类型：
--
作者：
Landrum LM;Brady WE;Armstrong DK;Moore KN;DiSilvestro PA;O'Malley DM;Tenney ME;Rose PG;Fracasso PM
确定 veliparib 联合 PLD 和卡铂 (CD) 在复发性铂敏感上皮性卵巢癌患者中的最大耐受剂量 (MTD) 和剂量限制毒性 (DLT)。确定 MTD 与贝伐珠单抗联合用药的耐受性。患者在第 1 天接受 PLD（30 mg/m2，IV）和卡铂（AUC 5，IV），并在第 1-7 天（间歇）或第 1-28 天（连续）接受 veliparib。基于第一个周期的 DLT 剂量递增阶段采用标准 3+3 设计。 MTD 确定后，将 6 名患者纳入每个贝伐单抗治疗方案（第 1 天和第 15 天 10 mg/kg）的队列，以评估可行性。 DLT 基于贝伐珠单抗队列的前 4 个治疗周期。在剂量递增阶段，27 名患者接受了 3 种剂量水平的治疗，其中 6 名患者出现 DLT，包括 4 级血小板减少症 (n=4) 和长期中性粒细胞减少症 >7 天 (n=3)。在 veliparib 的 MTD（两个给药组均为 80 mg p.o. b.i.d.）时，骨髓抑制是 DLT。在 MTD 时，另外 12 名患者接受了贝伐珠单抗治疗，其中 9 名患者经历了 DLT，包括 4 级血小板减少症 (n=4)、长期中性粒细胞减少症 >7 天 (n=1)、3 级高血压 (n=5) 和 5 级败血症 (n=1)。对于患有复发性铂敏感卵巢癌的女性，veliparib 联合 CD 的 MTD 为 80 mg PO BID。使用贝伐珠单抗时，12 名患者中有 9 名出现 DLT。与铂类疗法联合使用时，需要考虑较低剂量的 veliparib。
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of veliparib combined with PLD and carboplatin (CD) in patients with recurrent, platinum-sensitive epithelial ovarian cancer. To determine the tolerability at the MTD combined with bevacizumab. Patients received PLD (30 mg/m2, IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7 (intermittent) or days 1-28 (continuous). Standard 3+3 design was used in the dose escalation phase with DLTs based on the first cycle. Once the MTDs were determined, cohorts of 6 patients were enrolled to each regimen with bevacizumab (10 mg/kg on day 1 and 15) to assess feasibility. DLTs were based on the first 4 cycles of treatment in the bevacizumab cohorts. In the dose-escalation phase, 27 patients were treated at 3 dose levels with DLTs noted in 6 patients including grade 4 thrombocytopenia (n=4), and prolonged neutropenia >7 days (n=3). At the MTD of veliparib (80 mg p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At MTD, 12 additional patients were treated with bevacizumab with 9 patients experiencing DLTs including grade 4 thrombocytopenia (n=4), prolonged neutropenia >7 days (n=1), grade 3 hypertension (n=5), and grade 5 sepsis (n=1). The MTD of veliparib combined with CD is 80 mg PO BID in women with recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs were noted in 9 out of 12 patients. Lower doses of veliparib will need to be considered when given in combination with platinum-based therapies.