Drug–drug interactions (DDI) in oncology are of particular importance owing to the narrow therapeutic index and the toxicity of anticancer agents. Data are scarce in sarcoma patients (pts). We aimed to evaluate the frequency and severity of DDI with chemotherapy (CT) and tyrosine kinase inhibitor (TKI), identify the risk factors for DDI, and assess the impact of a pharmacist evaluation before anticancer treatment.
We performed a retrospective review of consecutive sarcoma pts starting CT (doxorubicin, ifosfamide, gemcitabine, trabectedin-based or other) or TKI (pazopanib or other). A pharmacist had prospectively performed medication reconciliation (MR). Potential DDI with antitumor drugs were identified and categorized (by using a 4-point scale) using Micromedex electronic software.
From 2014 to 2018, 122 soft-tissue and 80 bone sarcoma pts (103 males, median age 50 years, Q1-Q3 34-62) were included before CT (86%) or TKI (14%). The median number of medications was 3 (Q1-Q3 2-5), 65 pts (32%) had at least 5 drugs; 34 pts (17%) used complementary and alternative medicines (CAM). 37 potential DDI with severity classified as major, were identified. Univariate analysis identified number of drugs (p<0.001), performance status (p=0.04), pain (p = 0.002), antidepressant (p<0.001), proton pump inhibitors (PPI) (p<0.001) and TKI (p<0.001) as risk factors for DDI. TKI, PPI and antidepressant remained significant in multivariate analysis (p<0.02). Factors associated with CAM use were marital status (p=0.003) and ethnic origin (p= 0.03). A pharmacist performed 157 MR and made 71 interventions among 59 pts (24%) (34 drugs discontinued, 16 replacements, 2 dose adjustments, 19 drug monitoring). Pharmacist interventions were more frequent for TKI than for CT treated pts (63% versus 17%; p<0.001) and 29% of these interventions implied CAM.
Clinical interventions on DDI are more frequently required among sarcoma pts treating with TKI than CT. Medication review by a pharmacist is of crucial importance to prevent DDI with TKI. This review must consider not only traditional medication but also CAM, which are implied in a third of DDI in sarcoma pts.