BETHESDA, MD — Two drugs used in the treatment of several cancers have poorly understood drug-drug interactions that could have significant implications for patients. Erlotinib, which is used in lung cancer and pancreatic cancer treatment, and gefitinib, used in lung, breast and other cancers, are epidermal growth factor receptor tyrosine kinase inhibitors.
Previous studies indicated that concomitant use of EGFR-TKIs significantly inhibits the function of two very common drugs, fluoxetine and losartan, which could compound the health issues facing cancer patients by less effectively treating their depression and high blood pressure, respectively.
Based on those findings, a team of researchers at Walter Reed National Military Medical Center in Bethesda, MD., and Fort Belvoir Community Hospital in Fort Belvoir, Va., sought to better understand how the EGFR-TKIs interacted with a broader range of drugs. To do so, they partnered with MHS data experts who used data provided by the Joint Pathology Center of the DoD Cancer Registry, the comprehensive ambulatory/professional encounter record (CAPER) and the pharmacy data transaction service (PDTS) to identify patients treated for cancer and their comorbidities as well as the medications prescribed to those individuals.
The team categorized patients into two groups—those that completed treatment with erlotinib or gefitinib without recorded adverse effects and those who discontinued treatment with erlotinib or gefitinib and had recorded adverse effects or switched therapies. They then sorted the medications prescribed into those taken before or after treatment with the EGFR-TKIs and those taken concurrently.
Of the 348 patients with diagnosis data, 234 completed treatment and 114 discontinued treatment with erlotinib or gefitinib. A search showed pharmacy data for 240 patients for erlotinib and 18 for gefitinib. In total, 177 of these patients completed treatment and 81 discontinued it.
Patients in the completed treatment group filled between one and 75 drugs, with a range of 11 to 20 medications. Among those who discontinued treatment, between three and 103 drugs were filled, with a median of 31 to 40 medications. The team identified the 20 most commonly filled drugs that most often had side effects recorded in connection with use while being treated with erlotinib or gefitinib as well as the specific side effects noted.
While “this review cannot conclude that any drug resulted in erlotinib or gefitinib discontinuation,” the team said, “associations between top-filled drugs and side effects have been made.” The researchers encouraged proof of concept via in vitro laboratory testing with the identified drugs to better understand the interactions and clinical effects of use with erlotinib and gefitinib.
- Shou KJ, Louong TLT, Powers CN, Reinhardt BJ, McAnulty MJ, Weina PJ. Retrospective evaluation of erlotinib and gefitinib used in the military health system from the perspective of drug-drug interactions. 2023 ASCO annual meeting. June 2-6, 2023. J Clin Oncol 41, 2023 (suppl 16; abstr e15108)
