Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis.
Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis.
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DOI：
10.1002/onco.13822
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Crawford J
中科院分区：
文献类型：
--
作者：
Nielson CM;Bylsma LC;Fryzek JP;Saad HA;Crawford J
化疗引起的毒性导致治疗剂量减少或延迟，影响患者的治疗结果。这项系统评价和荟萃分析评估了相对剂量强度 (RDI) 对接受非辅助化疗方案的成年实体瘤患者生存的影响。在 PubMed、Embase 和 Web of Science 数据库中搜索了评估 RDI 与生存之间关系的同行评审英文期刊文章或国会摘要；观察性研究、≥20 名患者的病例系列以及 2013 年至 2020 年期间发表的临床试验均符合资格。在报告类似肿瘤类型、治疗方案和 RDI 的 OS 风险比 (HR) 的研究中，进行了荟萃分析，以量化 RDI 水平与总生存期 (OS) 之间的关联。森林图代表 HR 汇总和 95% 置信区间 (CI)； Cochran 的 Q 和 I2 检验评估了研究的异质性。总体而言，共审阅了 919 篇文章，纳入了 22 篇；七人有资格进行荟萃分析。对四项基于卡铂的乳腺癌、非小细胞肺癌或卵巢癌研究（HR 1.17；95% CI：1.07–1.27）和三项基于 FOLFOX、FOLFIRI 或 FOLFIRINOX 的结直肠癌或胰腺癌研究（HR 1.39；95% CI：1.03-1.89）。基于卡铂的方案（血小板减少：14%–22%；贫血：15%–19%；中性粒细胞减少：24%–58%）的 3 级或更高血液学毒性高于基于 FOLFOX、FOLFIRI 或 FOLFIRINOX 的方案（血小板减少：1%–4%；贫血：5%–19%；中性粒细胞减少症：19%–47%）。结果表明，两种方案的 RDI ≥80% 或 ≥85% 的 OS 较长，表明跨治疗方式的毒性管理可能有助于维持较高的 RDI 并有益于晚期实体瘤患者的生存。化疗引起的毒性导致剂量减少和/或治疗延迟，从而影响患者的治疗结果。这项系统评价和荟萃分析评估了相对剂量强度 (RDI) 对采用非辅助化疗方案的实体瘤患者生存的影响，结果表明，对于基于卡铂和基于 FOLFOX、FOLFIRI 或 FOLFIRINOX 的化疗方案的实体瘤患者，RDI 水平至少为 80% 的总生存期更长，表明维持 RDI ≥80% 或 ≥ ‐85% 具有保护作用。尽管在基于卡铂的研究中更多地发生 3 级或更高的血液学毒性，但管理治疗方案中的毒性可能有助于维持较高的 RDI 并最终有利于总体生存。化疗引起的毒性对癌症患者的最佳治疗和给药方案提出了挑战。本综述评估了相对剂量强度（包括剂量延迟和减少）对接受非辅助化疗的实体瘤患者生存的影响。
Chemotherapy‐induced toxicities lead to therapy dose reduction or delay, affecting patient outcomes. This systematic review and meta‐analysis evaluated the impact of relative dose intensity (RDI) on survival in adult patients with solid tumor cancer on nonadjuvant‐based chemotherapy regimens. PubMed, Embase, and Web of Science databases were searched for peer‐reviewed English journal articles or congress abstracts evaluating association between RDI and survival; observational studies, case series of ≥20 patients, and clinical trials published between 2013 and 2020 were eligible. Meta‐analyses were conducted to quantify the association between RDI levels and overall survival (OS) among studies reporting a hazard ratio (HR) for OS by similar tumor types, regimens, and RDI. Forest plots represented summary HR and 95% confidence interval (CI); Cochran's Q and I2 tests evaluated study heterogeneity. Overall, 919 articles were reviewed and 22 included; seven were eligible for meta‐analysis. Significantly shorter OS at RDI <80% versus ≥80% and <85% versus ≥85% was observed upon meta‐analysis of four carboplatin‐based studies for breast, non‐small cell lung, or ovarian cancer (HR 1.17; 95% CI: 1.07–1.27) and three FOLFOX‐, FOLFIRI‐, or FOLFIRINOX‐based studies for colorectal or pancreatic cancer (HR 1.39; 95% CI: 1.03–1.89). Grade 3 or higher hematologic toxicities were higher for carboplatin‐based regimens (thrombocytopenia: 14%–22%; anemia: 15%–19%; neutropenia: 24%–58%) than FOLFOX‐, FOLFIRI‐, or FOLFIRINOX‐based regimens (thrombocytopenia: 1%–4%; anemia: 5%–19%; neutropenia: 19%–47%). The results suggested longer OS with RDI ≥80% or ≥85% for both regimens, indicating that management of toxicities across treatment modalities may contribute to maintenance of higher RDI and benefit survival for patients with advanced solid tumors. Chemotherapy‐induced toxicities lead to dose reduction and/or treatment delay, thus affecting patient outcomes. Results of this systematic review and meta‐analysis, evaluating the impact of relative dose intensity (RDI) on survival of patients with solid tumors on nonadjuvant‐based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for patients with solid tumors on carboplatin‐based and FOLFOX‐, FOLFIRI‐, or FOLFIRINOX‐based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80% or ≥ ‐85%. Although grade 3 or higher hematologic toxicities occurred more in carboplatin‐based studies, managing toxicities across treatment regimens may contribute to maintenance of higher RDI and ultimately benefit overall survival. Chemotherapy‐induced toxicities are a challenge to optimal treatments and dosing regimens for cancer patients. This review evaluates the effect of relative dose intensity, including dose delays and reductions, on survival in patients with solid tumors receiving nonadjuvant‐based chemotherapy.
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