纳米颗粒白蛋白结合紫杉醇加卡铂作为 III-IV 期不可切除卵巢癌新辅助化疗的有效性和安全性:一项单臂、开放标签、Ib/II 期研究。

IF 7 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Lina Yin, Wei Jiang, Shuai Liu, Yi Fu, Lin Zhou, Xuan Pei, Shuang Ye, Wenbin Shen, Huijuan Yang, Boer Shan
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引用次数: 0

摘要

背景:卵巢癌(OC)患者的肿瘤不太可能被完全细胞减灭至无大体残留病灶(R0),或者不适合手术治疗,这时可以考虑采用新辅助化疗。这项Ib/II研究旨在评估纳米颗粒白蛋白结合型紫杉醇(nab-紫杉醇)加卡铂作为III-IV期不可切除卵巢癌新辅助化疗的有效性和安全性:这项Ib/II期研究招募了符合条件的III-IV期不可切除OC患者。所有患者均在手术前接受纳布-紫杉醇(260 mg/m2,第1天,每3周1次)加卡铂(AUC 5,第1天,每3周1次)的新辅助治疗3个周期,然后接受3-6个周期的辅助化疗。Ib期的主要终点是安全性;II期的主要终点是R0切除率。次要终点为无进展生存期(PFS)、总生存期(OS)、客观反应率(ORR)和安全性(针对所有人群):有62名患者入组,并在2019年10月至2020年12月期间接受了新辅助治疗,其中9人属于Ib期部分,53人属于II期部分。共有53名患者接受了手术,R0切除率为73.6%(95% CI,59.7-84.7%)。所有患者的中位随访时间为17.5个月(0.7-36.7个月),最佳ORR为83.9%(95% CI,71.7-92.4%),部分反应47例,中位PFS为18.6个月(95% CI,13.8-23.3%),未达到中位OS。在新辅助化疗期间,91.9%的患者(57/62)发生了任何级别的治疗相关不良事件(TRAEs)。最常见的血液学不良事件是中性粒细胞减少(55/62,88.7%),非血液学毒性是脱发(36/62,58.1%)。49名患者(79.0%)至少出现过一次3-4级TRAE,其中最常见的是中性粒细胞减少(44/62,71.0%)。此外,分别有9例(Ib期1例;II期8例)和7例(II期)患者因AE而延误了新辅助化疗和手术:该研究表明,新辅助化疗纳布紫杉醇加卡铂治疗III-IV期不可切除的OC具有令人鼓舞的疗效和可控的安全性。此外,在这种临床情况下,应谨慎考虑化疗和手术延迟导致的AE:试验注册:ClinicalTrials.gov,ChiCTR1900026893。注册时间:2019年10月25日。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy and safety of nanoparticle albumin-bound paclitaxel plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable ovarian cancer: a single-arm, open-label, phase Ib/II study.

Background: Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable OC.

Methods: Eligible patients with stage III-IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m2, day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3-6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations).

Results: Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7-84.7%). With a median follow-up of 17.5 (range 0.7-36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7-92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8-23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3-4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively.

Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting.

Trial registration: ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019.

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来源期刊
BMC Medicine
BMC Medicine 医学-医学:内科
CiteScore
13.10
自引率
1.10%
发文量
435
审稿时长
4-8 weeks
期刊介绍: BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.
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