Nielson Carrie M, Bylsma Lauren C, Fryzek Jon P, Saad Hossam A, Crawford Jeffrey
Amgen Inc., Thousand Oaks, California, USA.
EpidStrategies, A Division of ToxStrategies, Inc., Ann Arbor, Michigan, USA.
Oncologist. 2021 Sep;26(9):e1609-e1618. doi: 10.1002/onco.13822. Epub 2021 Jun 9.
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 I 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.
化疗引起的毒性反应会导致治疗剂量减少或延迟，从而影响患者的治疗效果。本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癌症患者生存的影响。
在PubMed、Embase和Web of Science数据库中检索评估RDI与生存之间关联的同行评审英文期刊文章或会议摘要；符合条件的是2013年至2020年发表的观察性研究、≥20例患者的病例系列以及临床试验。对报告了按相似肿瘤类型、方案和RDI划分的总生存（OS）风险比（HR）的研究进行荟萃分析，以量化RDI水平与OS之间的关联。森林图表示汇总HR和95%置信区间（CI）；Cochran's Q和I检验评估研究异质性。
总体而言，共审查了919篇文章，纳入22篇；7篇符合荟萃分析条件。对四项基于卡铂的乳腺癌、非小细胞肺癌或卵巢癌研究进行荟萃分析时，观察到RDI<80%与≥80%以及<85%与≥85%相比，OS显著缩短（HR 1.17；95%CI：1.07 - 1.27）；对三项基于FOLFOX、FOLFIRI或FOLFIRINOX的结直肠癌或胰腺癌研究进行荟萃分析时，观察到RDI<80%与≥80%以及<85%与≥85%相比，OS显著缩短（HR 1.39；95%CI：1.03 - 1.89）。基于卡铂的方案3级或更高等级血液学毒性高于基于FOLFOX、FOLFIRI或FOLFIRINOX的方案（血小板减少：14% - 22%；贫血：15% - 19%；中性粒细胞减少：24% - 58%）（血小板减少：1% - 4%；贫血：5% - 19%；中性粒细胞减少：19% - 47%）。
结果表明两种方案RDI≥80%或≥85%时OS更长，这表明跨治疗方式管理毒性反应可能有助于维持较高的RDI并使晚期实体瘤患者受益。
化疗引起的毒性反应会导致剂量减少和/或治疗延迟，从而影响患者的治疗效果。本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实体瘤患者生存的影响，结果表明接受基于卡铂和基于FOLFOX、FOLFIRI或FOLFIRINOX化疗方案的实体瘤患者，RDI水平至少为80%时总生存更长，这表明维持RDI≥80%或≥85%具有保护作用。尽管基于卡铂的研究中3级或更高等级血液学毒性发生率更高，但跨治疗方案管理毒性反应可能有助于维持较高的RDI并最终使总生存受益。
