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紫杉烷类单药治疗方案用于复发性上皮性卵巢癌。

Taxane monotherapy regimens for the treatment of recurrent epithelial ovarian cancer.

机构信息

Department of Natural Sciences, Middlesex University, London, UK.

Department of Medical Oncology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin 9, Ireland.

出版信息

Cochrane Database Syst Rev. 2022 Jul 12;7(7):CD008766. doi: 10.1002/14651858.CD008766.pub3.


DOI:10.1002/14651858.CD008766.pub3
PMID:35866378
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9309650/
Abstract

BACKGROUND: Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs. Currently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment. OBJECTIVES: To assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified. SELECTION CRITERIA: We included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence. DATA COLLECTION AND ANALYSIS: Two review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: Our literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool. We found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain. We found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants). When examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence). Quality-of-life data were not extractable from any of the included studies. AUTHORS' CONCLUSIONS: Fewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence). Three-weekly paclitaxel, given at a dose of 175 mg/m compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).

摘要

背景:卵巢癌是全球第七大常见癌症诊断,也是第八大癌症死亡原因。上皮性卵巢癌最为常见,占病例的 90%。上皮性卵巢癌患者的一线治疗包括细胞减灭术和基于铂类和紫杉烷类的化疗。然而,超过 50%的上皮性卵巢癌患者会复发,并需要进一步化疗,而且某些患者会对铂类药物产生耐药性。目前,对于上皮性卵巢癌复发的女性,关于大多数化疗药物(包括紫杉烷类药物)的使用指南尚不清楚。紫杉醇、拓扑替康、聚乙二醇脂质体多柔比星盐酸盐、曲贝替定和吉西他滨在英国均由临床医生酌情使用,并与女性讨论潜在的不良反应。紫杉烷类药物可以每周(剂量较低)或每三周(剂量较高)给药,这可能会导致不良反应和有效性的严重程度不同。由于复发性疾病提示不可治愈的疾病,因此,考虑副作用和治疗方案的影响,以及生活质量,而不仅仅是治疗的延长生命的效果,就显得尤为重要。

目的:评估不同紫杉烷类单药治疗复发性上皮性卵巢癌、输卵管或原发性腹膜癌的疗效和毒性。

检索方法:我们检索了 CENTRAL、MEDLINE 和 Embase,截至 2022 年 3 月 22 日。还检索了其他相关数据库和试验注册处以及灰色文献,但未发现其他研究。共确定了 1500 条记录。

选择标准:我们纳入了随机对照试验,这些试验将紫杉烷类单药治疗用于先前接受过铂类化疗的诊断为复发性上皮性卵巢癌、输卵管或原发性腹膜癌的成年女性。我们纳入了比较两种或多种紫杉烷类单药治疗方案的试验。参与者可以经历疾病的首次复发或任何一线复发。

数据收集和分析:两名综述作者筛选、独立评估研究,并从纳入的研究中提取数据。我们研究的临床结局包括总生存期、反应率、无进展生存期、神经毒性、中性粒细胞减少症、脱发和生活质量。我们按照标准 Cochrane 方法使用固定效应和随机效应模型进行了统计分析。我们根据 GRADE 方法评估证据的确定性。

主要结果:我们的文献检索产生了 1500 条记录,其中有 1466 项研究;通过搜索灰色文献或手检,没有发现其他研究。我们将检索结果上传到 Covidence。排除 92 条重复记录后,我们筛选了 1374 条记录的标题和摘要。其中,我们确定了 24 项符合全文筛选标准的研究。我们纳入了四项平行组随机对照试验(RCT)。所有试验均为多中心,并在医院环境中进行。这些研究包括 981 名符合条件的复发性上皮性卵巢癌、输卵管或原发性腹膜癌患者,中位年龄在 56 至 62 岁之间。所有参与者的世界卫生组织(WHO)体能状态均为 0 至 2 级。组织学中浆性成分的比例在 56%至 85%之间。参与者包括铂类敏感(71%)和铂类耐药(29%)复发的患者。一些参与者接受过紫杉烷预处理(5.6%),而大多数是紫杉烷初治患者(94.4%)。没有研究在 Cochrane 偏倚风险工具的任何领域被归类为高偏倚风险。我们发现每周紫杉醇与三周紫杉醇相比,总生存期(OS)可能差异不大,但证据非常不确定(风险比(RR)为 0.94,95%置信区间(CI)为 0.66 至 1.33,两项研究,263 名参与者,低质量证据)。同样,每周和三周紫杉醇之间的反应率(RR 为 1.07,95% CI 为 0.78 至 1.48,两项研究,263 名参与者,低质量证据)和无进展生存期(PFS)(RR 为 0.83,95% CI 为 0.46 至 1.52,两项研究,263 名参与者,低质量证据)也可能差异不大,但证据非常不确定。我们发现每周和三周紫杉醇方案之间的化疗相关不良事件存在差异。每周紫杉醇方案可能会降低中性粒细胞减少症的风险(RR 为 0.51,95% CI 为 0.27 至 0.95,两项研究,260 名参与者,低质量证据)和脱发(RR 为 0.58,95% CI 为 0.46 至 0.73,一项研究,205 名参与者,低质量证据)。神经毒性可能差异不大,但证据非常不确定,我们不能排除这种影响(RR 为 0.53,95% CI 为 0.19 至 1.45,两项研究,260 名参与者)。当检查三周紫杉醇方案中紫杉醇剂量的影响时,250 mg/m紫杉醇方案可能比 175 mg/m 方案引起更多的神经毒性(RR 为 0.41,95% CI 为 0.21 至 0.80,一项研究,330 名参与者,中等质量证据)。我们无法从纳入的任何研究中提取生活质量数据。

作者结论:与每周紫杉醇相比,每周紫杉醇可能会降低中性粒细胞减少症的风险(低质量证据),尽管可能对神经毒性的风险没有影响(极低质量证据)。这是基于参与者接受的药物剂量较低且频率较高。然而,我们对这一结果的信心较低,实际效果可能与对效果的估计有很大差异。每周紫杉醇可能会降低脱发的风险,尽管两个治疗组的脱发率都很高(46% 与 79%)(低质量证据)。每周紫杉醇可能会降低毒性的可能性,因为它可能对反应率(极低质量证据)、无进展生存期(极低质量证据)或总生存期(极低质量证据)没有负面影响。与较高剂量相比,每周紫杉醇可能会降低接受三周紫杉醇化疗方案的患者的神经毒性风险。我们对这一结果的置信度中等;实际效果可能接近对效果的估计,但也有可能存在显著差异。对于接受三周紫杉醇治疗的患者,如果使用较高剂量,将剂量降低至 175 mg/m 紫杉醇可能对无进展生存期或总生存期没有负面影响(极低质量证据)。

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