Survival Outcomes of Epithelial Ovarian Cancer Patients Following Dose-dense Versus 3-Weekly Platinum-Paclitaxel Chemotherapy: A Meta-Analysis

V Pergialiotis; E Liatsou; N Thomakos; M Liontos; M Frountzas; A Papapanagiotou; A Rodolakis; D Haidopoulos

doi:10.1016/j.clon.2022.10.015

Survival Outcomes of Epithelial Ovarian Cancer Patients Following Dose-dense Versus 3-Weekly Platinum-Paclitaxel Chemotherapy: A Meta-Analysis

Clin Oncol (R Coll Radiol). 2023 Feb;35(2):e189-e198. doi: 10.1016/j.clon.2022.10.015. Epub 2022 Nov 7.

Authors

V Pergialiotis¹, E Liatsou², N Thomakos², M Liontos³, M Frountzas⁴, A Papapanagiotou², A Rodolakis², D Haidopoulos²

Affiliations

¹ 1st Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: pergialiotis@yahoo.com.
² 1st Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
³ Department of Clinical Therapeutics, Division of Oncology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁴ 1st Department of Propaedeutic Surgery, "Hippocratio" General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

PMID: 36357255
DOI: 10.1016/j.clon.2022.10.015

Abstract

Aims: Dose-dense chemotherapy has proven its value in several cancer fields. The purpose of the present systematic review is to evaluate the impact of dose-dense chemotherapy on survival outcomes of epithelial ovarian cancer patients.

Materials and methods: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta and metafor functions. A sensitivity analysis was carried out to evaluate the possibility of small study effects and P-hacking. The methodological quality of the included studies was assessed using Risk of Bias 2 (RoB2) and Risk of Bias in non-Randomized Trials (RoBINS) tools.

Results: Overall, 12 studies were included in the present systematic review, involving 4979 epithelial ovarian cancer patients. The risk of recurrence was substantially improved in patients receiving dose-dense chemotherapy (hazard ratio 0.82, 95% confidence interval 0.70, 0.96); however, the result of the meta-analysis may be attributed to the effect size of smaller studies as following adjustment for small study effects the outcome becomes non-significant (hazard ratio 0.91, 95% confidence interval 0.81, 1.02, P = 0.123). Overall survival rates were not improved by dose-dense chemotherapy (hazard ratio 0.79, 95% confidence interval 0.60, 1.04). Thirty-five types of adverse effect were identified following retrieval of data from the original studies. Dose-dense chemotherapy did not increase significantly the rates of severe adverse effects, although thrombosis, severe diarrhoea and severe nausea were more prevalent in this group of patients.

Conclusion: Dose-dense chemotherapy is associated with comparable side-effects to those of standard chemotherapy; however, data related to survival outcomes are not positive; hence, its use outside the setting of clinical trials should be discouraged.

Keywords: Chemotherapy; dose-dense; meta-analysis; ovarian cancer.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols* / adverse effects
Carcinoma, Ovarian Epithelial* / drug therapy
Female
Humans
Ovarian Neoplasms* / drug therapy
Paclitaxel / therapeutic use
Platinum / therapeutic use
Proportional Hazards Models

Substances

Paclitaxel
Platinum