Long-term follow-up of sequential intravesical gemcitabine and docetaxel salvage therapy for non-muscle invasive bladder cancer

Chevuru, Phani T.; McElree, Ian M.; Mott, Sarah L.; Steinberg, Ryan L.; O’Donnell, Michael A.; Packiam, Vignesh T.

doi:10.1016/j.urolonc.2022.10.030

Cited by 21 publications

(20 citation statements)

References 15 publications

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“…Gemcitabine and docetaxel therapy seems to produce a more reliable initial response, although there is relatively consistent attrition over time. 28 …”

Section: Discussionmentioning

confidence: 99%

“…This interpretation is supported by results from previous studies that found lower benefit of BCG treatment among older adults who may be increasingly immunosenescent. Gemcitabine and docetaxel therapy seems to produce a more reliable initial response, although there is relatively consistent attrition over time …”

Section: Discussionmentioning

confidence: 99%

“…Gemcitabine and docetaxel therapy seems to produce a more reliable initial response, although there is relatively consistent attrition over time. 28 Treatment tolerability was historically a concern with BCG treatment, although with proper protocols and monitoring, the likelihood of experiencing major AEs from BCG induction therapy remains low. 10 Nevertheless, irritative lower urinary tract symptoms, such as hematuria, dysuria, urinary urgency or frequency, and UTIs, are common and can make BCG treatment adherence difficult.…”

Section: Jama Network Open | Urologymentioning

confidence: 99%

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Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer

et al. 2023

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ImportanceDue to the ongoing bacillus Calmette-Guérin (BCG) shortage, sequential intravesical gemcitabine and docetaxel has been increasingly used as first-line therapy for high-risk non–muscle-invasive bladder cancer (NMIBC). However, data directly comparing these 2 therapies are lacking.ObjectiveTo compare the outcomes of patients with high-risk NMIBC treated with gemcitabine and docetaxel vs BCG.Design, Setting, and ParticipantsThis retrospective cohort study was conducted from January 1, 2011, to December 31, 2021. The median (IQR) duration of follow-up was 23 (12-33) months for patients receiving gemcitabine and docetaxel and 49 (27-79) months for patients receiving BCG. All patients were treated at the University of Iowa tertiary care center. A total of 312 patients with high-risk treatment-naive NMIBC were included; 174 patients were treated with BCG therapy and 138 were treated with gemcitabine and docetaxel therapy.ExposuresAfter undergoing complete transurethral resection of bladder tumor, patients received either sequential intravesical gemcitabine, 1 g, and docetaxel, 37.5 mg, or 1 vial of BCG. Induction treatments were administered once per week for 6 weeks. Maintenance regimens were initiated if the patient was disease free at the first follow-up visit.Main Outcomes and MeasuresThe primary outcome was high-grade recurrence-free survival (RFS). Survival probabilities were estimated using the Kaplan-Meier method. Cox regression models were used to evaluate the association of covariates with outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events, version 5.ResultsAmong 312 patients, the median (IQR) age was 73 (66-79) years; 255 patients (81.7%) were male and 292 (93.6%) were White. Baseline clinicopathological characteristics such as sex, smoking status, and pretreatment tumor pathology were similar between treatment groups. High-grade RFS estimates were 76% (95% CI, 69%-82%) at 6 months, 71% (95% CI, 64%-78%) at 12 months, and 69% (95% CI, 62%-76%) at 24 months in the BCG group and 92% (95% CI, 86%-95%) at 6 months, 85% (95% CI, 78%-91%) at 12 months, and 81% (95% CI, 72%-87%) at 24 months in the gemcitabine and docetaxel group. Multivariable Cox regression analyses controlled for age, sex, treatment year, and presence of carcinoma in situ revealed that treatment with gemcitabine and docetaxel was associated with better high-grade RFS (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04) and RFS (hazard ratio, 0.56; 95% CI, 0.34-0.92; P = .02) than treatment with BCG. Induction therapy for BCG was associated with greater treatment discontinuation than induction therapy for gemcitabine and docetaxel (9.2% vs 2.9%; P = .02).Conclusions and RelevanceIn this cohort study, gemcitabine and docetaxel therapy was associated with less high-grade disease recurrence and treatment discontinuation than BCG therapy. These findings suggest that, while awaiting results from an ongoing randomized clinical trial during the current BCG shortage, use of gemcitabine and docetaxel can be considered for recommendation in updated practice guidelines.

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“…Gemcitabine and docetaxel therapy seems to produce a more reliable initial response, although there is relatively consistent attrition over time. 28 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Jama Network Open | Urologymentioning

confidence: 99%

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Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer

et al. 2023

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“…4 We recently published long-term outcomes for 97 patients in whom BCG failed, with median followup of 49 months, which showed 5-year HG-RFS of 30% and 5-year cancer-specific survival of 91%. 5 Importantly, none of these studies could identify any patient-, disease-, or prior treatmenterelated factors associated with Gem/Doce failure on multivariable analysis. [3][4][5] Receipt of maintenance Gem/Doce was the only variable associated with increased risk of recurrence.…”

mentioning

confidence: 99%

“…5 Importantly, none of these studies could identify any patient-, disease-, or prior treatmenterelated factors associated with Gem/Doce failure on multivariable analysis. [3][4][5] Receipt of maintenance Gem/Doce was the only variable associated with increased risk of recurrence. 4 Given these favorable findings, particularly with respect to consistent efficacy regardless of BCG failure type, we assessed how Gem/Doce compared with BCG-based regimens in patients with a single BCG failure who were not BCG unresponsive, and thus eligible for repeat BCG induction.…”

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Nonrisk-adapted Sequential Intravesical Gemcitabine and Docetaxel for Nonmuscle-invasive Bladder Cancer: The Time Is Now

2023

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Novel immunotherapeutic options for BCG‐unresponsive high‐risk non‐muscle‐invasive bladder cancer

Hannouneh,

Hijazi,

Alsaleem

et al. 2023

Cancer Medicine

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BackgroundHigh‐risk non‐muscle‐invasive bladder cancer (HR‐NMIBC) presents a challenge to many physicians due to its ability to resist Bacillus Calmette–Guérin (BCG) intravesical therapy and the substantial rate of progression into muscle‐invasive bladder cancer (MIBC). Patients who are BCG‐unresponsive have worse prognosis and thus require further management including radical cystectomy (RC), which significantly impacts quality of life. Moreover, the ongoing worldwide shortage of BCG warrants the need for policies that prioritize drug use and utilize alternative treatment strategies. Hence, there is a significant unmet need for bladder preserving therapy in this subset of patients.MethodsTo address this issue, we searched the relevant literature in PUBMED for articles published from 2019 through May of 2023 using appropriate keywords. All clinical trials of patients with HR‐NMIBC treated with immune‐related agents were retrieved from clinicaltrials.gov.Findings and Future PerspectivesExploratory treatments for BCG‐Unresponsive HR‐NMIBC included immune checkpoint inhibitors (ICI), oncolytic viral therapy, cytokine agonists, and other immunomodulators targeting TLR, EpCaM, FGFR, MetAP2, and IDO1. Some combination therapies have been found to work synergistically and are preferred therapeutically over monotherapy. Three drugs—pembrolizumab, valrubicin, and most recently, nadofaragene firadenovec‐vncg—have been FDA approved for the treatment of BCG‐unresponsive NMIBC in patients who are ineligible for or decline RC. However, all explored treatment options tend to postpone RC rather than provide long‐term disease control. Additional combination strategies need to be studied to enhance the effects of immunotherapy. Despite the challenges faced in finding effective therapies, many potential treatments are currently under investigation. Addressing the landscape of biomarkers, mechanisms of progression, BCG resistance, and trial design challenges in HR‐NMIBC is essential for the discovery of new targets and the development of effective treatments.

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Long-term follow-up of sequential intravesical gemcitabine and docetaxel salvage therapy for non-muscle invasive bladder cancer

Cited by 21 publications

References 15 publications

Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer

Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer

Nonrisk-adapted Sequential Intravesical Gemcitabine and Docetaxel for Nonmuscle-invasive Bladder Cancer: The Time Is Now

Novel immunotherapeutic options for BCG‐unresponsive high‐risk non‐muscle‐invasive bladder cancer

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