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 I² 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.