Real-world data on herb-drug interactions in oncology: A scoping review of pharmacoepidemiological studies

Abstract

Background: The concurrent use of conventional drugs and herbal medicines is becoming popular among patients with cancer. However, the potential risk of herb-drug interactions (HDI) remains under-addressed in the literature. Previous reviews have mainly focused on the prevalence of interactions, with less attention paid to the methods used by pharmacoepidemiological studies on evaluating HDI. This scoping review aims to summarize the existing pharmacoepidemiological studies that evaluate HDI using real-world data and to identify gaps to be addressed in future research.

Methods: A comprehensive search was performed in nine English- and Chinese-language databases from their inception to May 2021. Gray literature and manual searches were conducted to identify additional studies. The recommended components of the pharmacoepidemiological studies and key findings related to HDI were summarized. The proportion (%) of patients with cancer at risk of HDI was estimated by combining data from eligible studies.

Results: Twenty-eight studies were included in the review. More than half of these studies were cross-sectional studies (n = 18, 64.3%), followed by retrospective cohort studies (n = 5, 17.9%) and prospective cohort studies (n = 2, 7.1%). The three cancer drugs most commonly studied for their interaction potential with herbs were tamoxifen (n = 11, 39.3%), cyclophosphamide (n = 6, 21.4%), and paclitaxel (n = 6, 21.4%). Most cross-sectional studies identified potential HDI using tertiary databases and primary literature searches. Conversely, prospective and retrospective studies mainly investigated actual clinical outcomes, such as adverse events and secondary cancer occurrences. Most interaction outcomes identified using real-world data did not lead to negative clinical consequences. Collectively, 45.4% of herbal medicine users of the included studies were found to be at risk of HDI. We infer from this review that the common limitations of these studies were limited sample size, lack of data on herbal medicine use and details of HDI, and lack of evidence of HDI. Based on the study limitations, several recommendations to enrich the data sources and optimize the study designs were proposed.

Conclusions: There is a high demand for pharmacoepidemiological research on HDI, considering the increasing popularity of herbal medicine among patients with cancer. It is anticipated that emerging real-world data in this field can guide the development of safe and effective approaches to integrative oncology.

Keywords: Cancer; DDI, Drug-drug interactions; HDI, Herb-drug interactions; Herb-drug interaction; PD, Pharmacodynamics; PK, Pharmacokinetics; Pharmacoepidemiology; RCT, Randomized controlled trial; Real-world data; Scoping review.