{"title":"纳布-紫杉醇和卡铂治疗子宫上皮癌的 2 期可行性研究","authors":"","doi":"10.1016/j.ygyno.2024.07.682","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks.</p></div><div><h3>Methods</h3><p>Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (<span><span>NCT02744898</span><svg><path></path></svg></span>). Patients received 6 cycles of D1 nab-P 100 mg/m<sup>2</sup> IV with C AUC 6 IV and D8 nab-P 100 mg/m<sup>2</sup> IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods.</p></div><div><h3>Results</h3><p>From 08/2016–03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months.</p></div><div><h3>Conclusions</h3><p>The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.</p></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A phase 2 feasibility study of nab-paclitaxel and carboplatin in epithelial carcinoma of the uterus\",\"authors\":\"\",\"doi\":\"10.1016/j.ygyno.2024.07.682\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks.</p></div><div><h3>Methods</h3><p>Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (<span><span>NCT02744898</span><svg><path></path></svg></span>). Patients received 6 cycles of D1 nab-P 100 mg/m<sup>2</sup> IV with C AUC 6 IV and D8 nab-P 100 mg/m<sup>2</sup> IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods.</p></div><div><h3>Results</h3><p>From 08/2016–03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months.</p></div><div><h3>Conclusions</h3><p>The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.</p></div>\",\"PeriodicalId\":12853,\"journal\":{\"name\":\"Gynecologic oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gynecologic oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0090825824010461\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecologic oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0090825824010461","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景我们评估了在单臂前瞻性临床试验中完成6个周期的纳布-紫杉醇(nab-P)和卡铂(C)治疗晚期/复发性EC的可行性,以及第1天(D)、第8天纳布-P联合D1 C q3weeks的安全性和疗效。方法一项开放标签、单机构试验(NCT02744898)招募了既往未接触过铂/他蒽的早期、高风险、晚期原发性/复发性EC患者。患者接受了 6 个周期的 D1 nab-P 100 mg/m2 IV 与 C AUC 6 IV 和 D8 nab-P 100 mg/m2 IV q21D 治疗。试验采用单阶段设计,在α=0.05和功率=80%的条件下,用23名受试者测试了完成6个周期的受试者比例≤0.50的零假设和比例≥0.75的备择假设。完成 6 个周期的患者(主要结果)、客观反应率(ORR)和临床获益率(CBR)均以精确的 95% Clopper-Pearson 置信区间估算。无进展生存期(PFS)和总生存期(OS)采用 Kaplan-Meier 方法估算。19名患者(82.6%,95% CI:61.2%,95.0%)完成了6个周期,因此我们可以拒绝我们的空值。12名患者(52.2%)发生了≥1次3/4级治疗相关不良事件,包括:贫血,6例(26.1%);中性粒细胞减少,5例(21.7%);腹泻,3例(13.0%)。14名患者(60.1%)报告了1级神经病变。在9例出现可测量靶病灶的患者中,ORR为33.3%(95% CI:7.5%,70.1%),CBR为55.6%(95% CI:21.2%,86.3%)。晚期/复发性患者的中位 PFS 为 23.2 个月(95% CI:12.1,NR)。结论 nab-P/C D1,8 方案符合预先指定的可行性标准,毒性和疗效均可接受。使用nab-P可减少类固醇预处理的需要,这种卡铂双联疗法可能会在评估晚期EC与免疫检查点抑制剂联合治疗的试验中证明是有利的。
A phase 2 feasibility study of nab-paclitaxel and carboplatin in epithelial carcinoma of the uterus
Background
We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks.
Methods
Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods.
Results
From 08/2016–03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months.
Conclusions
The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.
期刊介绍:
Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published.
Research Areas Include:
• Cell and molecular biology
• Chemotherapy
• Cytology
• Endocrinology
• Epidemiology
• Genetics
• Gynecologic surgery
• Immunology
• Pathology
• Radiotherapy