Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta‐Analysis

BACKGROUND: 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. METHODS: 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(2) tests evaluated study heterogeneity. RESULTS: 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%). CONCLUSION: 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. IMPLICATIONS FOR PRACTICE: 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.