Advertisement

Multi-Institution Evaluation of Sequential Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guerin Naïve Patients with Non-Muscle Invasive Bladder Cancer

Published:September 14, 2022DOI:https://doi.org/10.1016/j.clgc.2022.09.004

      Highlights

      • Due to production shortages, BCG has been precluded from many urological practices.
      • Gem/Doce is a safe and effective treatment for NMIBC.
      • Further prospective evaluation is underway.

      Abstract

      Introduction

      : Single agent intravesical chemotherapy regimens have historically compared unfavorably to Bacillus Calmette-Guerin (BCG) as initial treatment following resection for patients with high-risk non-muscle invasive bladder cancer (NMIBC). However, there have been few reports of multi-agent intravesical chemotherapy regimens in this setting. Our objective is to determine the efficacy of sequential intravesical gemcitabine and docetaxel (Gem/Doce) in BCG naïve patients with NMIBC.

      Patients and Methods

      : Collaborating institutions retrospectively identified patients with NMIBC who were treated with Gem/Doce between 6/2009 and 5/2018. An sub-cohort of patients without prior BCG and treated with Gem/Doce was identified. Treatment consisted of 6 weekly instillations of gemcitabine (1 gram/50mL) followed immediately by docetaxel (37.5 mg/50mL). Maintenance was utilized at the discretion of the treating physician. Recurrence-free survival (RFS), progression (PFS), and overall survival (OS) were assessed. Treatment tolerance and discontinuation were also evaluated. Statistical analysis was descriptive in nature.

      Results

      : Sixty-five patients were treated, with median age 75 years and median follow-up of 15.2 months. 77% had high-grade disease and 40% had carcinoma in-situ (CIS). RFS was 82%, 76%, and 66% at 6, 12 and 24 months respectively. Amongst patients with high-grade disease, high-grade RFS was 85%, 78%, and 66% at 6, 12, and 24 months respectively. One patient progressed to muscle-invasive bladder cancer. Limitations include the retrospective study design, small cohort size, and lack of a comparator arm.

      Conclusion

      : Intravesical Gem/Doce may be an effective treatment for BCG naïve NIMBC and warrants further investigation.

      MicroAbstract

      : BCG is the gold-standard adjuvant treatment following TURBT for high-risk NMIBC. Unfortunately, ongoing production shortages have diminished BCG availability. In a multi-institutional retrospective cohort of 65 patients, we f 56098[mound sequential intravesical gemcitabine and docetaxel (Gem/Doce) provided significant relief of recurrence (66% RFS at 2-years) and was well-tolerated (97% finished a full induction). Prospective evaluation of Gem/Doce is underway.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Chang SS
        • Bochner BH
        • Chou R
        • et al.
        Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline.
        The Journal of urology. 2017; 198: 552-559
        • Sylvester RJ
        • van der Meijden APM
        • Lamm DL
        Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials.
        The Journal of urology. 2002; 168: 1964-1970
        • Lamm DL
        • Blumenstein BA
        • Crissman JD
        • et al.
        Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study.
        The Journal of urology. 2000; 163: 1124-1129
        • Yong C
        • Steinberg RL
        • O'Donnell MA
        Severe Infectious Complications of Intravesical Bacillus Calmette-Guerin: A Case Series of 10 Patients.
        Urology. 2020; 137: 79-83
        • Steinberg RL
        • Thomas LJ
        • Mott S
        • et al.
        Multi-Perspective Tolerance Evaluation of Bacillus Calmette-Guerin with Interferon in the Treatment of Non-Muscle Invasive Bladder Cancer.
        Bladder Cancer. 2019; 5
        • Joudi FN
        • Smith BJ
        • O'Donnell MA
        • et al.
        The impact of age on the response of patients with superficial bladder cancer to intravesical immunotherapy.
        The Journal of urology. 2006; 175: 1634-1640
        • Oddens JR
        • Sylvester RJ
        • Brausi MA
        • et al.
        The effect of age on the efficacy of maintenance bacillus calmette-guérin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: Results from EORTC genito-urinary group study 30911.
        European Urology. 2014; 66: 694-701
        • Solana R
        • Pawelec G
        • Tarazona R
        Aging and Innate Immunity.
        Immunity. 2006; 24: 491-494
        • Herr HW
        • Dalbagni G
        Intravesical bacille Calmette-Guérin (BCG) in immunologically compromised patients with bladder cancer.
        BJU International. 2013; 111: 984-987
        • Palou J
        • Angerri O
        • Segarra J
        • et al.
        Intravesical bacillus Calmette-Guerin for the treatment of superficial bladder cancer in renal transplant patients.
        Transplantation. 2003; 76: 1514-1516
        • Babjuk M
        • Burger M
        • Comperat EM
        • et al.
        European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update.
        European urology. 2019; 76: 639-657
      1. Flanigan RC, Edney MT, Maddox-Smith A, et al: BCG Shortage Info. American Urological Association 2019: 1. Available at: https://www.auanet.org/about-us/bcg-shortage-info.

      2. Messing EM: The BCG Shortage.
        Bladder Cancer. 2017; 3: 227-228
        • Gontero P
        • Marini L
        • Frea B
        Intravesical gemcitabine for superficial bladder cancer: Rationale for a new treatment option.
        BJU International. 2005; 96: 970-976
        • Skinner EC
        • Goldman B
        • Sakr WA
        • et al.
        SWOG S0353: Phase II trial of intravesical gemcitabine in patients with nonmuscle invasive bladder cancer and recurrence after 2 prior courses of intravesical bacillus calmette-guérin.
        Journal of Urology. 2013; 190: 1200-1204
        • Abal M
        • Andreu JM
        • Barasoain I
        Taxanes: microtubule and centrosome targets, and cell cycle dependent mechanisms of action.
        Current cancer drug targets. 2003; 3: 193-203
        • Barlow LJ
        • McKiernan JM
        • Benson MC
        Long-term survival outcomes with intravesical docetaxel for recurrent nonmuscle invasive bladder cancer after previous bacillus Calmette-Guérin therapy.
        Journal of Urology. 2013; 189: 834-839
        • Schlack K
        • Boegemann M
        • Steinestel J
        • et al.
        The safety and efficacy of gemcitabine for the treatment of bladder cancer.
        Expert review of anticancer therapy. 2016; 16: 255-271
        • De Wit R
        • Kruit WHJ
        • Stoter G
        • et al.
        Docetaxel (Taxotere): An active agent in metastatic urothelial cancer; Results of a phase II study in non-chemotherapy-pretreated patients.
        British Journal of Cancer. 1998; 78: 1342-1345
        • Steinberg RL
        • Thomas LJ
        • Brooks N
        • et al.
        Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer.
        The Journal of urology. 2019; (101097JU0000000000000688)
        • McElree IM
        • Steinberg RL
        • Martin AC
        • et al.
        Sequential Intravesical Gemcitabine and Docetaxel for BCG-Naïve High-Risk Non-Muscle Invasive Bladder Cancer. PD26-03.
        Journal of Urology. 2022; 207: e488
        • Davies BJ
        • Hwang TJ
        • Kesselheim AS
        Ensuring Access to Injectable Generic Drugs - The Case of Intravesical BCG for Bladder Cancer.
        The New England journal of medicine. 2017; 376: 1401-1403
        • Pandey R
        • Jackson JK
        • Liggins R
        • et al.
        Enhanced taxane uptake into bladder tissues following co-administration with either mitomycin C, doxorubicin or gemcitabine: association to exfoliation processes.
        BJU International. 2018; 122: 898-908
        • Bohle A
        • Jocham D
        • Bock PR
        Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity.
        The Journal of urology. 2003; 169: 90-95
        • Malmström P-U
        • Sylvester RJ
        • Crawford DE
        • et al.
        An Individual Patient Data Meta-Analysis of the Long-Term Outcome of Randomised Studies Comparing Intravesical Mitomycin C versus Bacillus Calmette-Guérin for Non–Muscle-Invasive Bladder Cancer.
        European Urology. 2009; 56: 247-256
        • Justin M
        • Roger L
        • Neema N
        • et al.
        MP43-04 CONTEMPORARY OUTCOMES OF NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS TREATED WITH INDUCTION BCG.
        Journal of Urology. 2019; 201 (e618–e618)
        • Grimm M-O
        • van der Heijden T
        • Colombel M
        • et al.
        Treatment of high-grade non-muscle invasive bladder carcinoma by standard number and dose of BCG instillations versus reduced number and standard dose of BCG instillations: Results of the phase III clinical trial (NIMBUS).
        Journal of Clinical Oncology. 2020; 38: 436
        • Lamm DL
        • Blumenstein BA
        • Crawford ED
        • et al.
        A Randomized Trial of Intravesical Doxorubicin and Immunotherapy with Bacille Calmette–Guérin for Transitional-Cell Carcinoma of the Bladder.
        New England Journal of Medicine. 1991; 325: 1205-1209
        • Lamm DL
        • Blumenstein BA
        • David Crawford E
        • et al.
        Randomized intergroup comparison of bacillus calmette-guerin immunotherapy and mitomycin C chemotherapy prophylaxis in superficial transitional cell carcinoma of the bladder a southwest oncology group study.
        Urologic Oncology: Seminars and Original Investigations. 1995; 1: 119-126
        • Lee S
        • Lim B
        • You D
        • et al.
        Association of Bacillus Calmette-Guerin shortages with bladder cancer recurrence: A single-center retrospective study.
        Urologic oncology. 2020;