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

Autor: Wilson NR; Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX., Wiele AJ; Division of Cancer Medicine, Unive rsity of Texas MD Anderson Cancer Center, Houston, TX., Surasi DS; Department of Nuclear Imaging, Division of Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX., Rao P; Department of Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., Sircar K; Department of Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., Tamboli P; Department of Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., Shah AY; Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., Genovese G; Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., Karam JA; Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX; Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., Wood CG; Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX., Tannir NM; Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: pmsaouel@mdanderson.org., Msaouel P; Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: ntannir@mdanderson.org.
Jazyk: angličtina
Zdroj: Clinical genitourinary cancer [Clin Genitourin Cancer] 2021 Dec; Vol. 19 (6), pp. e401-e408. Date of Electronic Publication: 2021 Sep 15.
DOI: 10.1016/j.clgc.2021.08.007
Abstrakt: 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 January 2005 and September 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/m 2 and doxorubicin at 40-50 mg/m 2 intravenously every 2 weeks. Three patients (18.8%) achieved partial response and 7 (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.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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