Efficacy and safety of gemcitabine plus doxorubicin in patients with renal medullary carcinoma

ABSTRACT Introduction : Renal medullary carcinoma (RMC) is a rare and lethal renal cell carcinoma characterized by the loss of tumor suppressor SMARCB1. Molecular profiling studies have suggested that RMC cells may be vulnerable to therapies that generate DNA damage, such as the combination of the nucleoside analog gemcitabine and topoisomerase inhibitor doxorubicin. Patients and Methods : We retrospectively analyzed the records of patients with RMC treated with gemcitabine plus doxorubicin at our institution between 01/2005 and 09/2020. Best radiographic response and disease progression (RECIST v1.1) were assessed by a blinded radiologist. Results : Sixteen patients were included in the study. All but 1 patient (93.8%) received prior platinum-based chemotherapy. Gemcitabine was given intravenously at 900-1200 mg/m2 and doxorubicin at 40-50 mg/m2 intravenously every two weeks. Three patients (18.8%) achieved partial response and seven (43.8%) patients achieved stable disease. The median progression-free survival was 2.8 months (95% CI, 0-6.0). Median overall survival (OS) from gemcitabine plus doxorubicin initiation was 8.1 months (95% CI 4.6-11.7) and OS from diagnosis was 15.5 months (95% CI 4.2-26.8 months). There were no grade ≥ 4 AEs; grade 3 AEs were cytopenias (18.8%), nausea (12.5%), fatigue (12.5%), and cardiotoxicity (6.2%). No somatic alterations were detected in the 9 patients tested by targeted next generation sequencing assays. Conclusion : Gemcitabine plus doxorubicin was well tolerated and demonstrated clinical activity in patients with platinum-refractory RMC, with a subset of patients experiencing durable responses lasting longer than 6 months. Further investigation is warranted to determine biomarkers of sensitivity and target mechanisms of resistance. MicroAbstract Renal medullary carcinoma (RMC) is commonly treated with platinum-based chemotherapy. We retrospectively analyzed sixteen patients with RMC treated with gemcitabine plus doxorubicin, finding median progression-free survival 2.8 months (95% CI, 0-6.0), and median overall survival 8.1 months (95% CI 4.6-11.7). Therapy was well tolerated, with clinical activity in patients with platinum-refractory RMC; some experiencing durable responses longer than 6 months.