Intravesical bacillus-Calmette Guérin (BCG) is the traditional gold-standard treatment of intermediate- and high-risk nonmuscle-invasive bladder cancer (NMIBC); however, BCG therapy is fraught with frequent drug shortages and its scarcity has prompted investigation into alternative regimens. Furthermore, more than 30% of patients will experience cancer recurrence after BCG, and these patients are left with a paucity of effective second-line therapies. Intravesical gemcitabine and docetaxel (GemDoce) has emerged over the last few years as a promising therapeutic option for these patients.

Historically, patients with NMIBC receiving single agent intravesical chemotherapy have fared worse when compared to patients receiving BCG.¹ However, a strategy of multiagent chemotherapy can be extrapolated and rationalized from its systemic use for many cancers. Intravesical GemDoce was first described in 2014 by Steinberg et al.² The administration protocol involves a 6-week induction course of intravesical administration of 1 gm gemcitabine followed by 37.5 mg docetaxel. Monthly maintenance for 2 years is recommended for responders.³ The exposure of urothelium to gemcitabine has been demonstrated to result in improved subsequent taxane uptake.⁴ The initial 2014 report of GemDoce demonstrated 34% 2-year recurrence-free survival in a heavily pre-treated heterogeneous cohort of patients with varying degrees of post-BCG cancer recurrence. The safety and efficacy of GemDoce was subsequently corroborated in a large multi-institutional report of 276 patients with prior BCG exposure, which demonstrated 52% high-grade recurrence-free survival.^2,5 The regimen was well tolerated with <10% of patients requiring modifications in treatment schedule. Interestingly, in contrast to BCG, there were no identified clinicopathological or prior treatment related factors associated GemDoce failure.

To assess current utilization of GemDoce in North America, a cross-sectional, web-based survey was distributed via the Society of Urologic Oncologists (SUO) and Canadian Urologic Oncology Group (CUOG) mailing lists. In this survey provider prescribing patterns, including the preferred setting of GemDoce use, annual prescribing rate and description of barriers to administration of GemDoce, were assessed. The survey was distributed to 982 addresses (661 reporting bladder cancer in their practice). A total of 198 participants completed the survey (30% response rate for target audience), of whom 141 (71%) endorsed prescribing GemDoce over the last 12 months. The most common cohort that GemDoce was prescribed to was patients with BCG-unresponsive NMIBC with or without carcinoma in situ (67%), followed by those with BCG naïve high-risk NMIBC (25%) and primary treatment of intermediate-risk NMIBC (15%; Fig. 1). Based on conservative estimates of participant responses, at least 1,300 patients within the practices of the surveyed urologists are being prescribed GemDoce for NMIBC on an annual basis (Fig. 2). Notably, 44% of participants endorsed at least 1 barrier to prescribing or administering GemDoce at their institution. The most common barriers were problems with clinical workflow (ie clinic space to administer the drug), challenges with getting the hospital pharmacy to supply the drug, challenges with identifying who would benefit most from this regimen and cost. Results from this cross-sectional web-based survey demonstrate that GemDoce is being widely utilized among urologic oncologists for several disease states of NMIBC.

Figure 1. Disease setting(s) in which GemDoce is prescribed. CIS, carcinoma in situ.

Figure 2. Utilization of GemDoce.

Based on the promising data regarding GemDoce in BCG-unresponsive disease and the ongoing BCG shortage, GemDoce has been investigated for BCG-naïve NMIBC. A retrospective study from the University of Iowa recently reported results for 107 patients with BCG-naïve high-risk NMIBC treated with GemDoce, demonstrating 84% 2-year high-grade recurrence-free survival and <1% Grade 3 or higher toxicity.⁶ A Phase 2 prospective, single-arm clinical trial evaluating GemDoce for BCG-naïve high-grade NMIBC was initiated at the Johns Hopkins Greenberg Bladder Cancer Institute. Thus far, 24 patients have enrolled, with 15 patients completing their 3-month cystoscopic evaluation and 9 patients completing their 12-month evaluation. There have been no cancer recurrences on GemDoce therapy as well as no Grade 3+ or dose-limiting toxicities. These data have confirmed the data published in retrospective series, and have renewed interest in potentially using GemDoce as an alternative to BCG during periods of BCG shortage. Currently, a Phase 3 randomized, controlled trial comparing BCG vs GemDoce for high-grade NMIBC (BRIDGE Study) has been approved for funding through the National Cancer Institute National Clinical Trials Network and is in late-stage development.

For those interested in introducing GemDoce into their urology practices, please reach out to Dr. Packiam at vignesh-packiam@uiowa.edu or Dr. Kates at mkates@jhmi.edu.