taxanes

紫杉烷
  • 文章类型: Journal Article
    目的:该研究调查了冷冻疗法在减轻化疗引起的周围神经病变(CIPN)中的疗效,化疗的不良反应,通常导致剂量减少或治疗中断。
    方法:本研究注册于PROSPERO(CRD42023428936)。使用PubMed进行了文献检索,Embase,和Cochrane图书馆数据库。纳入研究冷冻疗法对CIPN影响的随机和非随机对照试验进行系统评价和荟萃分析。预防的主要结果是CIPN的发生率。
    结果:我们确定了17项试验,涉及2,851例患者。总的来说,11项试验比较了冷冻治疗组和对照组的CIPN发生率。观察到化疗中点和结束时CIPN的发生率存在显着差异,风险比(RR)为0.23(95%置信区间[CI]=0.13至0.43)和0.54(95%CI=0.33至0.88),分别。冷冻疗法也显著降低了感觉CIPN的发生率,RR为0.67(95%CI=0.49至0.92)。此外,冷冻治疗显示妇科癌症患者CIPN的发生率显著降低(RR=0.24,95%CI=0.14~0.41).化疗后的整体生活质量评分明显良好(标准化平均差=1.43;95%CI=0.50至2.36),冷冻治疗可缓解神经性症状。
    结论:冷冻疗法对CIPN的发展具有明显的预防作用,为接受化疗的患者提供实质性的症状缓解和生活质量改善。通过使用冷冻手套和袜子进行冷冻治疗,或连续流冷却系统,最佳在化疗前15分钟开始,并在化疗后15分钟结束,被推荐用于实现最大的治疗效果。
    OBJECTIVE: The study investigates cryotherapy\'s efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to dosage reduction or treatment discontinuation.
    METHODS: The study was registered with PROSPERO (CRD42023428936). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. Randomized and nonrandomized controlled trials that investigated the effects of cryotherapy on CIPN were included for systematic review and meta-analysis. The primary outcome for prevention was the incidence of CIPN.
    RESULTS: We identified 17 trials involving 2,851 patients. In total, 11 trials compared the incidence of CIPN between cryotherapy and control groups. Significant differences in the incidence of CIPN at the midpoint and end of chemotherapy were observed, with risk ratios (RRs) of 0.23 (95% confidence interval [CI] = 0.13 to 0.43) and 0.54 (95% CI = 0.33 to 0.88), respectively. Cryotherapy also significantly reduced the incidence of sensory CIPN, with an RR of 0.67 (95% CI = 0.49 to 0.92). Additionally, cryotherapy demonstrated a significant reduction in the incidence of CIPN in patients with gynecological cancers (RR = 0.24, 95% CI = 0.14 to 0.41). Significantly favorable global quality of life scores following chemotherapy (standardized mean difference = 1.43; 95% CI = 0.50 to 2.36) and relieved neuropathic symptoms were found with cryotherapy.
    CONCLUSIONS: Cryotherapy demonstrates a pronounced preventive effect against the development of CIPN, providing substantial symptomatic relief and quality of life improvements for patients undergoing chemotherapy. The administration of cryotherapy through the use of frozen gloves and socks, or continuous-flow cooling systems, optimally initiated 15 min prior to and concluded 15 min following chemotherapy, is recommended for achieving maximum therapeutic efficacy.
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  • 文章类型: Journal Article
    Taxanes,如紫杉醇和多西他赛,改变了乳腺癌治疗的前景,在早期和晚期/转移性疾病的化疗方案中发挥关键作用。虽然这些药物在提高患者预后方面表现出显著疗效,它们还与一系列可能影响治疗耐受性和生活质量的不良反应有关.这篇全面的综述为紫杉烷治疗乳腺癌提供了深入的探索,重点关注临床观点和毒性特征。我们描述了紫杉烷的作用机制,它们在各种乳腺癌亚型中的临床有效性,以及临床实践中常见的不良反应。此外,我们根据个体患者特征和治疗目标,研究减轻紫杉烷相关毒性并优化治疗选择和排序的策略.最后,我们强调未来研究和发展的领域,包括开发新的配方,识别治疗反应的预测性生物标志物,以及探索联合疗法以增强治疗效果。通过合并现有证据和临床见解,这篇综述旨在让临床医师和研究者了解紫杉烷治疗乳腺癌的现状,并指导进一步加强患者护理和预后的努力.
    Taxanes, such as paclitaxel and docetaxel, have transformed the landscape of breast cancer treatment, playing pivotal roles in chemotherapy protocols for both early-stage and advanced/metastatic diseases. While these agents have demonstrated remarkable efficacy in enhancing patient outcomes, they are also linked to a range of adverse effects that can impact treatment tolerability and quality of life. This comprehensive review offers an in-depth exploration of taxane therapy in breast cancer, with a focus on clinical perspectives and toxicity profiles. We delineate the mechanisms of action of taxanes, their clinical effectiveness across various breast cancer subtypes, and the prevalent adverse effects encountered in clinical practice. Moreover, we deliberate on strategies for mitigating taxane-associated toxicity and optimizing treatment selection and sequencing based on individual patient characteristics and therapeutic objectives. Finally, we underscore areas for future research and advancement, encompassing the development of novel formulations, the identification of predictive biomarkers for treatment response, and the exploration of combination therapies to bolster therapeutic outcomes. By amalgamating existing evidence and clinical insights, this review aims to apprise clinicians and researchers of the current status of taxane treatment in breast cancer and steer endeavors toward further enhancing patient care and outcomes.
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  • 文章类型: Systematic Review
    背景:目前的临床指南认可在妊娠头三个月后使用紫杉烷类药物。然而,关于其在产科和新生儿结局方面的安全性的证据有限.
    方法:使用MEDLINE进行了全面的文献检索,CENTRAL和WebofSciences数据库从成立到2022年12月16日。合格标准包括妊娠紫杉烷的使用,介绍原始发现,和提供的个案数据。进行了描述性统计分析。
    结果:共有159例患者在妊娠期接受紫杉烷治疗,导致162个胎儿在子宫内暴露。大多数患者患有乳腺癌(n=88;55.3%)或宫颈癌(n=45;28.3%)。最常用的紫杉烷是紫杉醇(n=131;82.4%)。共有111例(69.8%)患者在怀孕期间也接受了其他细胞毒性药物治疗,包括铂盐(n=70;63.0%)和阿霉素/环磷酰胺(n=20;18.0%)。虽然大多数患者在妊娠中期接受紫杉烷类药物(n=79;70.0%),两个人在孕早期接触紫杉烷。产科结果报告105例(66.0%),最常见的不良事件是早产或胎膜早破(n=12;11.4%),先兆子痫/HELLP综合征(n=6;5.7%),和羊水过少/羊水过少(n=6;5.7%)。所有具有妊娠结局的病例均导致活产(n=132)。总的来说,72例(54.5%)新生儿早产,40人(30.3%)被归类为小于胎龄(SGA),和2(1.5%)在5分钟时的Apgar评分<7。围产期并发症包括急性呼吸窘迫综合征(n=14;10.6%),高胆红素血症(n=5;3.8%),和低血糖(n=2;1.5%)。此外,报告先天性畸形7例(5.3%)。在16个月的中位随访中,后代健康状况为86(65.2%),其中13人(15.1%)有并发症,包括延迟的言语发展,复发性中耳炎,和急性髓细胞性白血病.
    结论:紫杉类药物在妊娠头三个月后似乎是安全的,产科和胎儿结局与一般产科人群相似。未来的研究应旨在确定在妊娠期间使用的最有效的紫杉烷方案和剂量。特别关注治疗安全。
    BACKGROUND: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited.
    METHODS: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken.
    RESULTS: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia.
    CONCLUSIONS: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety.
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  • 文章类型: Journal Article
    紫杉烷类在癌症治疗中与超敏反应的显著发生率相关,这可能会阻止他们在需要一线治疗的患者中使用。药物脱敏可诱导短暂的免疫耐受,并允许紫杉烷类药物在高度过敏的患者中重新引入。增加紫杉烷类药物给药过程中过敏反应(HSR)的知识。关于紫杉烷HSR快速药物脱敏(RDD)的安全性和有效性的系统评价。该研究遵循了系统评价和荟萃分析(PRISMA)指南的首选报告项目,在PROSPERO(CRD42021242324)注册,并在Medline进行了全面搜索,Embase,WebofScience和Scopus数据库。确定了25项研究,涵盖了10个国家,976例初始HSR患者接受紫杉醇(n=707)和多西他赛(n=284),总共进行了2396次脱敏。最常见的症状是紫杉醇的皮肤(74.6%)和多西他赛的呼吸(72.6%)。严重的初始超敏反应,包括过敏反应分别发生在39.6%和13%的紫杉醇和多西他赛病例中,以及第一次(87.4%)或第二次(81.5%)暴露期间。32.2%的紫杉醇治疗患者和20.6%的多西他赛治疗患者对RDD和突破反应(BTR)的耐受性良好。前用药包括皮质类固醇,抗组胺药和白三烯受体拮抗剂。最常用的方案是BWH3袋12个步骤,所有方案的成功率都在95-100%之间,没有死亡报告。RDD是紫杉烷类HSR患者的安全有效程序,应将方案标准化以广泛实施。
    Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.
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  • 文章类型: Journal Article
    化疗通常是过早卵巢功能不全和不孕症的原因,因为卵泡对化疗药物的作用极为敏感。具有不同作用机制的不同化学治疗剂可能会不同地损害卵巢功能。紫杉烷被广泛应用于临床肿瘤治疗,但具体的生殖毒理学信息仍有争议。本文就紫杉烷类药物对女性卵巢功能的影响及持续时间进行综述,并分析得出不同结论的可能原因。此外,对紫杉烷类药物对卵巢功能的毒性作用及其可能的作用机制进行了探讨。还综述了紫杉烷类引起的卵巢损伤的潜在保护策略和药物。
    Chemotherapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicles are extremely sensitive to the effects of chemotherapeutic agents. Different chemotherapeutic agents with varying mechanisms of action may damage ovarian function differently. Taxanes are widely used in clinical cancer treatment, but the specific reproductive toxicological information is still controversial. This review described the impact and duration of taxanes on ovarian function in women and analyzed the possible reasons for different conclusions. Furthermore, the toxicity of taxanes on ovarian function and its possible mechanisms were discussed. The potential protective strategies and agents against ovarian damage induced by taxanes are also reviewed.
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  • 文章类型: Journal Article
    氟嘧啶加铂(FP)和紫杉烷加铂(TP)是食管癌(EC)的标准治疗方法。本系统评价和荟萃分析旨在探讨FP和TP方案在EC患者治疗效果和毒性方面的差异。PubMed,Embase,和Cochrane进行了全面搜索和分析,以找到截至2022年3月22日接受FP和TP方案治疗的EC患者的相关文章。31项研究,共有3432名参与者,包括在这次审查中。主要结果显示,对于接受确定性放化疗治疗的EC患者,TP组的预后和治疗效果优于FP组(3年OS:RR:1.25,95%CI:1.08-1.44,p=0.003;3年PFS:RR:1.43,95%CI:1.17-1.75,p=0.0006;ORR:RR:1.17,95%CI:1.06-1.29,p=0.001。然而,TP治疗与白细胞减少和血小板减少的发生率显著相关(p<0.05)。术前新辅助放化疗组,两组生存时间相似(p>0.05)。FP方案对应于较高的血小板减少症发生率,而TP方案与发热性白细胞减少的发生率增加相关(p<0.05)。因此,在接受确定性放化疗的EC患者中,与FP方案相比,TP方案可产生更好的临床反应和生存益处。
    Fluoropyrimidine plus platinum (FP) and taxanes plus platinum (TP) are standard treatments for esophageal cancer (EC). This systematic review and meta-analysis aim to explore the difference in the therapeutic effect and toxicity of FP and TP regimens in EC patients. PubMed, Embase, and Cochrane were fully searched and analyzed to find relevant articles on EC patients treated with FP and TP regimens up to 22 March 2022. Thirty-one studies, with a total of 3432 participants, were included in this review. The primary outcomes showed that the prognosis and therapeutic efficacy of TP groups were better than those of FP groups for the EC patients treated with definitive chemoradiotherapy treatment (3-year OS: RR: 1.25, 95% CI: 1.08−1.44, p = 0.003; 3-year PFS: RR: 1.43, 95% CI: 1.17−1.75, p = 0.0006; ORR: RR: 1.17, 95% CI: 1.06−1.29, p = 0.001). However, TP therapy was significantly correlated with a higher incidence of leukopenia and thrombocytopenia (p < 0.05). In the preoperative neoadjuvant chemoradiotherapy group, these two groups had a similar survival time (p > 0.05). The FP regimen corresponded to a higher incidence of thrombocytopenia, while the TP regimen was associated with an increased incidence of febrile leukopenia (p < 0.05). Therefore, TP regimens could generate both superior clinical response and survival benefits when compared with FP regimens in EC patients undergoing definitive chemoradiotherapy.
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  • 文章类型: Journal Article
    目的:硬皮病是紫杉烷类药物治疗中罕见的并发症。尽管紫杉烷类引起的硬皮病的个别病例已被报道,对临床表现和治疗结果进行回顾和总结很少。这项研究报道了一名患者在紫杉醇治疗输尿管癌后出现弥漫性硬皮病和可能的硬皮病肾危象。
    方法:纳入了截至2022年4月发表的紫杉烷类引起的硬皮病病例的PubMed文献综述进行分析。
    结果:搜索确定了27名具有足够分析信息的患者。在28名患者中,包括这里介绍的,22是女性除一名患者外,外周水肿是所有患者中最常见的症状,并常伴有红斑11.症状通常在第4个疗程内发生在一半的患者中。皮肤病变逐渐进展为皮肤纤维化,向近端延伸。内脏器官受累并不常见。有时抗核抗体检测呈阳性,但是抗Scl70和抗着丝粒通常是阴性的。紫杉类药物治疗停止,在21、3和4名患者中持续且不可用,分别。15例患者使用或不使用免疫抑制药物治疗皮肤病变的皮质类固醇。在25名具有皮肤预后的患者中,19改进接受或未接受皮肤治疗的患者之间皮肤无明显改善(62.5%vs.75.0%,p=0.37)。停止紫杉烷类后皮肤通常会改善。
    结论:紫杉烷引起的硬皮病不同于特发性硬皮病。医生应该意识到这种情况,以便提供早期诊断并应用适当的管理,以避免严重皮肤硬化引起的严重并发症。•硬皮病是紫杉烷类治疗的一种罕见但独特且严重的并发症•皮肤表现和分布与特发性硬皮病相似,但是血管现象,内脏器官受累和硬皮病相关自身抗体很少出现。皮肤改善通常在停止紫杉烷类后不久发生•免疫抑制疗法在治疗紫杉烷类引起的硬皮病中的作用尚不清楚。
    OBJECTIVE: Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer.
    METHODS: A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis.
    RESULTS: The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes.
    CONCLUSIONS: Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear.
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  • 文章类型: Journal Article
    背景:纳米颗粒-白蛋白结合型紫杉醇(Nab-P)对乳腺癌患者常规紫杉烷类的长期益处仍存在争议。我们对研究进行了系统评价,以确定临床实践中选择的最佳紫杉烷类药物。
    方法:我们招募了患有乳腺癌的成年人(年龄≥18岁),将Nab-P(任何剂量)与常规紫杉醇或多西他赛进行比较,提供了有关生存数据的信息,响应率,或不良事件,是随机对照试验,病例对照研究,或队列研究,并以英文出版(包括在线出版的,在印刷出版物之前)。使用Cochrane协作工具和纽卡斯尔-渥太华量表进行偏倚风险评估。建议评估的分级,发展,并采用评价方法对证据质量进行评价。结果包括总体反应率,病理完全缓解率,无进展生存期,总生存率,过敏反应,白细胞减少症,中性粒细胞减少症,和感觉神经病变。
    结果:共20项合格临床研究,包括11,046例患者纳入分析。基于对无进展生存期(PFS)的漏斗图的目视检查,未观察到明显的发表偏倚,总生存率(OS)。与常规紫杉烷类组(n=2,743)相比,Nab-P组(n=1,680)的ORR(RR=1.21,95%CI:1.07-1.37;P=0.003)和pCR(RR=1.33,95%CI:1.17-1.51;P<0.001)明显更高。Nab-P组的疾病进展和死亡风险也低于常规紫杉烷组(HR=0.89,P=0.269)。此外,与常规紫杉烷组相比,Nab-P组治疗相关的过敏反应较少(RR=0.74,95%CI:0.59~0.93;P=0.009),且≥4级中性粒细胞减少(RR=0.39,95%CI:0.20~0.77;P=0.007)较少.Nab-P组任何级别的中性粒细胞减少症和感觉神经病变的发生率均明显高于常规紫杉烷组(分别为P=0.009和P<0.001)。
    结论:Nab-P在各阶段乳腺癌患者中的疗效和耐受性均明显优于常规紫杉烷类药物。此外,未来的研究应探讨降低Nab-P诱发的感觉神经病变发生率的预防策略.
    BACKGROUND: Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic review of studies to identify the optimal taxanes for selection in clinical practice.
    METHODS: We enrolled studies if they enrolled adults (age ≥18) with breast cancer, compared Nab-P (at any dose) to conventional paclitaxel or docetaxel, provided information on survival data, the response rate, or adverse events, were randomized controlled trials, case-control studies, or cohort studies, and were published in English (including those published online, ahead of the print publication). Cochrane Collaboration tool and Newcastle-Ottawa scale were used for bias-risk assessment. Grading of recommendations assessment, development, and evaluation approach were adopted for the quality of evidence evaluation. The outcomes included the overall response rate, pathological complete response rate, progression-free survival, overall survival, allergic reaction, leukopenia, neutropenia, and sensory neuropathy.
    RESULTS: A total of 20 eligible clinical studies comprising 11,046 patients were included in the analysis. No significant publication bias was observed based on a visual inspection of the funnel plots for progressionfree survival (PFS), and overall survival (OS). Compared to the conventional taxanes group (n=2,743), the Nab-P group (n=1,680) had a significantly higher ORR (RR =1.21, 95% CI: 1.07-1.37; P=0.003) and pCR (RR =1.33, 95% CI: 1.17-1.51; P<0.001). The Nab-P group also had a lower risk of disease progression and death than the conventional taxanes group (HR =0.89, P=0.269). Additionally, the Nab-P group had fewer treatment-related allergic reactions (RR =0.74, 95% CI: 0.59-0.93; P=0.009) and less grade ≥4 neutropenia (RR =0.39, 95% CI: 0.20-0.77; P=0.007) than the conventional taxanes group. The incidence of any-grade of neutropenia and sensory neuropathy were significantly higher in the Nab-P group than the conventional taxanes group (P=0.009 and P<0.001, respectively).
    CONCLUSIONS: The Nab-P in all stages of breast cancer patients had significantly better efficacy and tolerance than the conventional taxanes. Moreover, preventive strategies for reducing the incidence of Nab-P induced sensory neuropathy should be explored in future studies.
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  • 文章类型: Journal Article
    Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an innovative form of taxane that has superior antitumor effects; however, the safety profile between nab-paclitaxel and traditional taxanes remains controversial.
    To determine the burden of adverse events (AEs) in patients with multiple malignancies receiving nab-paclitaxel compared with that in patients receiving traditional taxanes.
    Randomized clinical trials comparing nab-paclitaxel with traditional taxanes (solvent-based paclitaxel [sb-paclitaxel] or docetaxel) in the treatment of primary solid-organ malignancies were included if AEs were reported as an outcome. Statistical analyses were conducted to calculate the summary odds ratio (OR) of the relevant adverse outcomes related to nab-paclitaxel and traditional taxanes. Prespecified subgroup analyses based on intervention and doses, primary tumor sites, and different ethnic groups were also performed.
    Twelve clinical trials were included in the meta-analysis. Grade 3/4 anemia, thrombocytopenia, and neurotoxicity were more frequent with nab-paclitaxel than with traditional taxanes. Nab-paclitaxel at 100 or 125 mg/m2/w dosage was associated with fewer or similar grade 3/4 specific AEs. Allergy was less common with nab-paclitaxel. The median recovery times of neurotoxicity were 25, 64, and 37 days in patients receiving nab-paclitaxel, sb-paclitaxel, and docetaxel, respectively. Elevated incidences of specific AEs were more common in breast cancer and non-Asian patients than in other malignancies and ethnic groups, respectively.
    Nab-paclitaxel increased the risk of hematologic and non-hematologic AEs in general, but anaphylaxis was less common, and the recovery duration of neurotoxicity was shorter. Weekly administration of nab-paclitaxel at a lower dosage provided better tolerance.
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  • 文章类型: Journal Article
    在过去的二十年里,转移性前列腺癌的治疗取得了重大进展。具有不同作用机制的多种治疗方法改善了转移性去势抵抗性前列腺癌(mCRPC)患者的临床结果,包括紫杉烷化疗。免疫疗法,强效雄激素受体途径抑制剂(ARPI),和放射性药物(镭-223)。由于这些治疗方法已经进入标准临床实践,临床医生在如何最佳选择和排序方面面临挑战,因为确立其疗效的里程碑式研究是使用安慰剂或最低限度有效治疗的对照组,并且缺乏前瞻性试验来检查治疗排序.最近,这种情况变得更加复杂,因为早期使用多西他赛和ARPI同时使用标准性腺睾酮抑制剂,已显示可显著改善去势敏感性前列腺癌患者的疾病控制和生存率.随着新疗法进入临床实践,如聚(ADP-核糖)聚合酶抑制剂和前列腺特异性膜抗原(PSMA)靶向治疗,在缺乏经过验证的预测性生物标志物的情况下,如何最佳选择和排序可用的治疗将是一个持续的难题.这篇综述将总结支持在mCRPC中使用每种活性剂的文献。我们将提出一个框架,该框架将指导基于先前疗法选择合适的药物,疾病特征和生物标志物。
    Over the last two decades, there has been significant progress in the treatment of metastatic prostate cancer. Multiple treatments with diverse mechanisms of action have improved clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) including taxane chemotherapy, immunotherapy, potent androgen receptor pathway inhibitors (ARPI), and radiopharmaceuticals (radium-223). As these treatments have entered standard clinical practise, clinicians have been challenged on how to optimally select and sequence them as the landmark studies establishing their efficacy had control arms with placebo or minimally effective therapy and there is a paucity of prospective trials examining treatment sequencing. More recently, the situation has been further complicated as the earlier up-front use of docetaxel and ARPI with standard gonadal testosterone inhibition has been shown to impart substantial improvements in disease control and survival for patients with castration sensitive prostate cancer. As new therapies enter into clinical practise such as the inhibitors of Poly (ADP-Ribose) Polymerase and Prostate Specific Membrane Antigen (PSMA)-targeted therapy, how to optimally select and sequence available treatments will be a continued dilemma in the absence of validated predictive biomarkers. This review will summarize the literature supporting the use of each active agent in mCRPC. We will propose a framework which will guide the selection of appropriate agents based on prior therapies, disease characteristics and biomarkers.
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