Long-term Clinical Outcomes of a Phase I Trial of Intravesical Docetaxel in the Management of Non–muscle-invasive Bladder Cancer Refractory to Standard Intravesical Therapy

Abstract

OBJECTIVES To report the long-term clinical outcomes and durability of response after treatment with induction intravesical docetaxel. Most novel agents used to treat bacillus Calmette-Guerin refractory high-grade non–muscle-invasive (NMI) bladder cancer are evaluated only after short follow-up periods. Our previously published phase I trial demonstrated that docetaxel is a safe agent for intravesical therapy with minimal toxicity and no detectable systemic absorption. We sought to determine long-term clinical outcomes after treatment with intravesical docetaxel. METHODS Eighteen patients with recurrent Ta (n = 7), T1 (n = 5), and Tis (n = 6) transitional cell carcinoma who experienced treatment failure with at least 1 prior intravesical therapy completed the phase I trial. Docetaxel was administered as 6 weekly intravesical instillations using a dose-escalation model terminated at 0.75 mg/mL. Efficacy was evaluated by interval cystoscopy with biopsies when indicated, cytology, and computed tomography imaging. Follow-up consisted of quarterly cystoscopy, cytology, computed tomography, and biopsy when indicated. RESULTS With a median follow-up of 48.3 months, 4 patients (22%) have demonstrated a complete durable response and currently remain disease-free without further treatment. Three patients (17%) had a partial response, defined as a single NMI recurrence with no further therapy for bladder cancer. Eleven patients (61%) failed treatment, and required another intervention. One patient developed stage progression. No delayed toxicities were noted. The median disease-free survival time was 13.3 months. CONCLUSIONS After 4 years of follow-up without maintenance therapy, intravesical docetaxel has demonstrated the ability to prevent recurrence in a select number of patients with refractory NMI bladder cancer and warrants further investigation.

Alternative therapies in patients with non-muscle invasive bladder cancer

“…Laudano et al [23] reported the clinical outcomes of a phase I trial of intravesical use of docetaxel as 6 weeks induction therapy in patients with at least one course of failed BCG therapy. Of 18 patients, 4 patients had demonstrated complete, and 3 patients partial responses; whereas 11 patients had failed treatment without significant toxicity after a median follow-up of 48.3 months.…”

Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

“…6,9,117 Long-term clinical outcomes in this cohort revealed 22% and 17% complete and partial response rates, respectively, while 61% failed treatment at a median follow-up of 48.3 months. 118 In a recent update of their series of 33 patients with refractory NMIBC, Barlow et al reported a 61% complete response rate after six weeks of induction therapy, and one-and two-year recurrence-free survival rates were 45% and 32%, respectively. 119 Taxoids are attractive candidates for intravesical therapy due to their potency, high molecular …”

The optimal management of T1 high-grade bladder cancer

“…Other combinations of intravesical agents are currently being evaluated. 42,43 Some patients that are candidates for cystectomy are not suitable for radical surgery because of the presence of comorbid medical illnesses or because they refuse surgery even after extended discussion of the risks. In these circumstances, alternative strategies are available but with a guarded success rate.…”