Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non–Muscle-Invasive Bladder Cancer

No AccessJournal of UrologyAdult Urology1 Nov 2022Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non–Muscle-Invasive Bladder CancerThis article is commented on by the following:Editorial CommentEditorial Comment Ian M. McElree, Vignesh T. Packiam, Ryan L. Steinberg, Sarah L. Mott, Paul T. Gellhaus, Kenneth G. Nepple, and Michael A. O'Donnell Ian M. McElreeIan M. McElree https://orcid.org/0000-0001-9991-4301 Carver College of Medicine, University of Iowa, Iowa City, Iowa , Vignesh T. PackiamVignesh T. Packiam Department of Urology, University of Iowa, Iowa City, Iowa , Ryan L. SteinbergRyan L. Steinberg Department of Urology, University of Iowa, Iowa City, Iowa , Sarah L. MottSarah L. Mott Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa , Paul T. GellhausPaul T. Gellhaus Department of Urology, University of Iowa, Iowa City, Iowa , Kenneth G. NeppleKenneth G. Nepple Department of Urology, University of Iowa, Iowa City, Iowa , and Michael A. O'DonnellMichael A. O'Donnell *Correspondence: University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, Iowa 52242 telephone: 1-319-356-2421; email: E-mail Address: [email protected] Department of Urology, University of Iowa, Iowa City, Iowa View All Author Informationhttps://doi.org/10.1097/JU.0000000000002848AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Intravesical gemcitabine-docetaxel has emerged as an efficacious and well-tolerated salvage therapy for non–muscle-invasive bladder cancer. However, further rescue therapies are needed for subsequent recurrences or intolerance, particularly when cystectomy is refused or precluded. Valrubicin is a U.S. Food and Drug Administration-approved agent for bacillus Calmette-Guérin unresponsive disease, yet as monotherapy has demonstrated poor efficacy. We report our experience with sequential intravesical valrubicin and docetaxel as a rescue therapy for non–muscle-invasive bladder cancer. Materials and Methods: We retrospectively identified all patients with recurrent non–muscle-invasive bladder cancer treated with valrubicin and docetaxel between April 2013 and June 2021. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. If disease-free at first follow-up, monthly maintenance of 2 years was initiated. The primary outcome was recurrence-free survival, assessed using the Kaplan-Meier method. Results: The analysis included 75 patients with median follow-up of 21 months (IQR: 13-37). Twelve patients with low-grade disease had a 73% recurrence-free survival at 2 years. Sixty-three patients with recurrent high-grade disease had a 38% 2-year high-grade recurrence-free survival. Forty-two (56%) patients had carcinoma in situ present; recurrence-free survival was similar for those with and without carcinoma in situ (P = .63). Two patients died of metastatic bladder cancer while 10 underwent cystectomy. Among patients with high-grade disease, overall, cancer-specific, and cystectomy-free survivals were 87%, 96%, and 84% at 2 years, respectively. Adverse events included bladder spasms (n = 18), urinary frequency (n = 10), and dysuria (n = 8). Two patients could not tolerate valrubicin and docetaxel induction. Conclusions: In a heavily pretreated population, our results suggest valrubicin and docetaxel is an effective rescue treatment for patients with recurrent non–muscle-invasive bladder cancer. Further prospective evaluation is needed. References 1. . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. Google Scholar 2. . Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016; 196(4):1021-1029. Link, Google Scholar 3. . Long-term results of intravesical therapy for superficial bladder cancer. Urol Clin North Am. 1992; 19(3):573-580. Google Scholar 4. , . Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol. 1987; 137(2):220-224. Link, Google Scholar 5. . Sequential intravesical gemcitabine and docetaxel for the salvage treatment of non-muscle invasive bladder cancer. Bladder Cancer. 2015; 1(1):65-72. Google Scholar 6. . Multi-institution evaluation of sequential gemcitabine and docetaxel as rescue therapy for nonmuscle invasive bladder cancer. J Urol. 2020; 203(5):902-909. Link, Google Scholar 7. . Intravesical sequential gemcitabine and docetaxel versus bacillus Calmette-Guerin (BCG) plus interferon in patients with recurrent non-muscle invasive bladder cancer following a single induction course of BCG. Urol Oncol Semin Original Invest. 2022; 40(1):9.e1-9.e7. Google Scholar 8. . Sequential intravesical gemcitabine and docetaxel for BCG-naïve high-risk non-muscle invasive bladder cancer. Poster presented at Society of Urologic Oncology Annual Meeting; December 2, 2021; Orlando, Florida https://suo-abstracts.secure-platform.com/a/gallery/rounds/12/details/1539. Google Scholar 9. . Contemporary outcomes of patients with nonmuscle-invasive bladder cancer treated with bacillus Calmette-Guérin: implications for clinical trial design. J Urol. 2021; 205(6):1612-1621. Link, Google Scholar 10. . Systematic review and cumulative analysis of perioperative outcomes and complications after robot-assisted radical cystectomy. Eur Urol. 2015; 67(3):376-401. Google Scholar 11. . Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009; 55(1):164-174. Google Scholar 12. . The current landscape of salvage therapies for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer. Curr Opin Urol. 2021; 31(3):178-187. Google Scholar 13. . Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol. 2000; 163(3):761-767. Link, Google Scholar 14. . Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021; 22(7):919-930. Google Scholar 15. . Definitions, end points, and clinical trial designs for non–muscle-invasive bladder cancer: recommendations from the international bladder cancer group. J Clin Oncol. 2016; 34(16):1935-1944. Google Scholar 16. U.S. Food and Drug Administration. Valrubicin prescribing information. Accessed December 29, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020892s019lbl.pdf. Google Scholar 17. Docetaxel (Taxotere) injection, for intravenous use: prescribing information. Accessed August 11, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020449s084lbl.pdf. Google Scholar 18. . MP08-18 Added value of a restaging procedure beyond the standard of care in the surveillance of non-muscle invasive bladder cancer. J Urol. 2018; 199(4S):e103. Link, Google Scholar 19. . Systematic review of factors associated with the utilization of radical cystectomy for bladder cancer. Eur Urol Oncol. 2019; 2(2):119-125. Google Scholar 20. . Does early cystectomy improve the survival of patients with high risk superficial bladder tumors?J Urol. 2001; 166(4):1296-1299. Link, Google Scholar 21. . Survival outcomes of early versus deferred cystectomy for high-grade non-muscle-invasive bladder cancer: a systematic review. Curr Urol. 2020; 14(2):66-73. Google Scholar 22. . Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer. Cancer. 2010; 116(8):1893-1900. Google Scholar 23. . Randomized phase III trial on gemcitabine versus mytomicin in recurrent superficial bladder cancer: evaluation of efficacy and tolerance. J Clin Oncol. 2010; 28(4):543-548. Google Scholar 24. . Combination intravesical chemotherapy for non–muscle-invasive bladder cancer. Eur Urol Focus. 2018; 4(4):503-505. Google Scholar Submitted February 11, 2022; accepted June 23, 2022; published July 5, 2022. Support: This work was supported in part by the John & Carol Walter Family Foundation, the Cancer Center Support Grant, and the Summer Research Fellowship provided by the Carver College of Medicine. Conflict of Interest: Michael O'Donnell: Abbott: research funding, consulting; Photocure: travel, consulting; Fidia: consulting; Merck: consulting; Theralase: consulting; Urogen: consulting; Vaxiion. Vignesh Packiam: Cold Genesys: consulting. Ethics Statement: This study received Institutional Review Board approval (IRB No. 201404766). Editor's Note: This article is the second of 5 published in this issue for which Category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1168 and 1169. © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology10 Aug 2022Editorial CommentJournal of Urology10 Aug 2022Editorial Comment Volume 208Issue 5November 2022Page: 969-977Supplementary Materials PEER REVIEW REPORTS Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.Keywordsvalrubicinurinary bladder neoplasmsdocetaxelMetricsAuthor Information Ian M. McElree Carver College of Medicine, University of Iowa, Iowa City, Iowa More articles by this author Vignesh T. Packiam Department of Urology, University of Iowa, Iowa City, Iowa More articles by this author Ryan L. Steinberg Department of Urology, University of Iowa, Iowa City, Iowa More articles by this author Sarah L. Mott Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa More articles by this author Paul T. Gellhaus Department of Urology, University of Iowa, Iowa City, Iowa More articles by this author Kenneth G. Nepple Department of Urology, University of Iowa, Iowa City, Iowa More articles by this author Michael A. O'Donnell Department of Urology, University of Iowa, Iowa City, Iowa *Correspondence: University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, Iowa 52242 telephone: 1-319-356-2421; email: E-mail Address: [email protected] More articles by this author Expand All Submitted February 11, 2022; accepted June 23, 2022; published July 5, 2022. Support: This work was supported in part by the John & Carol Walter Family Foundation, the Cancer Center Support Grant, and the Summer Research Fellowship provided by the Carver College of Medicine. Conflict of Interest: Michael O'Donnell: Abbott: research funding, consulting; Photocure: travel, consulting; Fidia: consulting; Merck: consulting; Theralase: consulting; Urogen: consulting; Vaxiion. Vignesh Packiam: Cold Genesys: consulting. Ethics Statement: This study received Institutional Review Board approval (IRB No. 201404766). Editor's Note: This article is the second of 5 published in this issue for which Category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1168 and 1169. Advertisement PDF downloadLoading ...