Rifampin may decrease the efficacy of crizotinib in lung cancer treatment

Abstract

Dear Editor: Crizotinib is an anticancer drug that acts as an anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibitor, and it has been shown to have marked therapeutic efficacy in treating advanced nonsmall cell lung cancer harboring ALK rearrangement in clinical trials. The median progression free survival (PFS) was 10.9 months, significantly longer than in chemotherapy group. Crizotinib has been approved by the U.S. Food and Drug Administration (FDA) since 2011. In Taiwan, it has been approved as a first-line drug for advanced adenocarcinoma harboring ALK rearrangement since November 2017. However, crizotinib is a CYP3A substrate, and the coadministration of crizotinib and a strong CYP3A inducer such as rifampin may decrease the plasma concentration of crizotinib and decrease its efficacy. A 66-year-old male patient presented to our hospital due to progressive dyspnea for 2 weeks. Chest radiography showed right pleural effusion, and chest computed tomography showed a contrast-enhanced 6.2-cm consolidated mass in the right upper lobe (Figure 1A,D). A bronchoscopic biopsy proved advanced lung adenocarcinoma. In addition, his specimen also showed immunoreactivity to ALK using D5F3 clone antibodies. He was given oral crizotinib 250 mg twice daily from March 19, 2018. A follow-up chest X-ray 2 weeks later showed dramatic resolution of the effusion and primary lung tumor (Figure 1B). Meanwhile, respiratory specimens yielded positive Mycobacteria Growth Indicator Tube (MGIT) results, and a diagnosis of pulmonary tuberculosis was made. Therefore, the standard combination of antituberculosis medicines (ethambutol + isoniazid + rifampin + pyrazinamide) was initiated on April 2, 2018. Unfortunately, his lung cancer worsened with recurrence of accumulated effusion 2 months later (Figure 1d). Because it was suspected that drug interactions had decreased the efficacy of crizotinib, we replaced crizotinib with alectinib 600 mg twice daily from June 21, 2018. His lung tumor and pleural effusion then markedly improved (Figure 1F), and the efficacy lasted for at least 6 months (Figure 1c). To the best of our knowledge, this is the first case to describe a patient with both lung cancer and tuberculosis in whom the coadministration of crizotinib and rifampin may have decreased the efficacy of crizotinib. Taiwan is an endemic area for tuberculosis, and the occurrence of both lung cancer and tuberculosis is possible. Rifampin is themost important first-line antituberculosis drug, however it is also a potent inducer of the cytochrome