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

• Published in: Urology (Ridgewood, N.J.) N.J.), 2010-01, Vol.75 (1), p.134-137
• Main Authors: Laudano, Melissa A, Barlow, Lamont J, Murphy, Alana M, Petrylak, Daniel P, Desai, Manisha, Benson, Mitchell C, McKiernan, James M
• Format: Article
• Language: English
• Subjects: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Carcinoma, Transitional Cell - drug therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Taxoids - administration & dosage; Time Factors; Treatment Failure; Urinary Bladder Neoplasms - drug therapy; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2009.06.112

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.