Carrie M Nielson 1 , Lauren C Bylsma 2 , Jon P Fryzek 3 , Hossam A Saad 1 , Jeffrey Crawford 4 Show Affiliations »
Abstract
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 solid-tumor cancer patients 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─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, 914 articles were reviewed and 37 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80 vs ≥80% and <85% vs ≥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/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/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 in solid tumor cancer patients on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for solid tumor cancer patients on carboplatin-based and FOLFOX-/FOLFIRI/FOLFIRINOX-based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80 or ≥85%. While 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. © AlphaMed Press 2021.
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 solid-tumor cancer patients 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─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, 914 articles were reviewed and 37 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80 vs ≥80% and <85% vs ≥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 /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 /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 in solid tumor cancer patients on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for solid tumor cancer patients on carboplatin -based and FOLFOX -/FOLFIRI /FOLFIRINOX -based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80 or ≥85%. While 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. © AlphaMed Press 2021.
Entities: Chemical
Disease
Gene
Species
Keywords:
(MeSH terms; 4-6): Carboplatin-based regimens; FOLFOX-FOLFIRI-based regimens; meta-analysis; overall survival; progression-free survival; relative dose intensity
Year: 2021
PMID： 33973301 DOI： 10.1002/onco.13822
Source DB: PubMed Journal: Oncologist ISSN： 1083-7159