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. 2021 Dec;19(6):e401-e408.
doi: 10.1016/j.clgc.2021.08.007. Epub 2021 Sep 15.

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

Nathaniel R Wilson  1 , Andrew J Wiele  2 , Devaki Shilpa Surasi  3 , Priya Rao  4 , Kanishka Sircar  4 , Pheroze Tamboli  4 , Amishi Y Shah  5 , Giannicola Genovese  6 , Jose A Karam  7 , Christopher G Wood  8 , Nizar M Tannir  9 , Pavlos Msaouel  10
Affiliations

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

Nathaniel R Wilson et al. Clin Genitourin Cancer. 2021 Dec.

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 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/m2 and doxorubicin at 40-50 mg/m2 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.

Keywords: Gemcitabine plus doxorubicin; Platinum-based chemotherapy; Renal cell carcinoma; Renal medullary carcinoma; SMARCB1.

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Conflict of interest statement

Conflict of Interest Disclosure:

AYS has received honoraria for service on scientific advisory boards for Pfizer, Exelixis, BMS, Roche, and Eisai; and research funding from BMS, Eisai, and EMD Serono. JAK has received honoraria for service on scientific advisory boards for Pfizer, Merck, and Roche/Genentech; institutional research funding from Roche/Genentech, Mirati Therapeutics, Merck, and Elypta; and holds stock ownership from Allogene, MedTek, and ROM technologies. NMT has received honoraria for service on scientific advisory boards for Bristol-Myers Squibb, Eli Lilly and Company, Exelixis, Inc., and Nektar Therapeutics; for strategic council meetings with Eisai Inc.; steering committee meetings with Pfizer, Inc.; and for seminar presentations for Ono Pharmaceutical Co., Ltd.; as well as research funding for clinical trials from Exelixis, Inc., Calithera Biosciences, and Nektar. PM has received honoraria for service on scientific advisory boards for Mirati Therapeutics, Bristol-Myers Squibb, and Exelixis; consulting for Axiom Healthcare Strategies; non-branded educational programs supported by Exelixis and Pfizer; and research funding for clinical trials from Takeda, Bristol-Myers Squibb, Mirati Therapeutics, Gateway for Cancer Research, and UT MD Anderson Cancer Center. All other authors (NRW, AJW, SDS, PR, KS, PT, GG, CGW) have nothing to disclose.

Figures

Figure 1.
Figure 1.
Waterfall Plot of best overall response, sorted by number of therapies before gemcitabine + doxorubicin. Three patients achieved PR, seven patients achieved SD, and three patients (*) did not meet PD per RECIST v1.1 but clinically had disease progression. PR, partial response; SD, stable disease; PD, progressive disease.
Figure 2.
Figure 2.
Duration of gemcitabine plus doxorubicin. All 16 patients were included in this swimmer plot for duration of therapy, sorted by number of therapies before gemcitabine plus doxorubicin. PR, partial response, SD, stable disease.
Figure 3.
Figure 3.
(A) Progression-free survival. (B) Overall survival from treatment initiation with gemcitabine plus doxorubicin. The shaded areas represent the 95% confidence bands for each curve. CI, Confidence interval.
See this image and copyright information in PMC

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