Sequential gemcitabine and docetaxel proves efficacious in NMIBC

Sequential intravesical instillations of gemcitabine and docetaxel are safe, well tolerated, and efficacious for preventing recurrence of non–muscle-invasive bladder cancer (NMIBC) in patients with disease recurrence after BCG failure, according to recent findings. Investigators in the multi-institutional retrospective study reported the results during the 2020 American Urological Association Virtual Experience.¹

The study² included 76 patients representing a heavily pretreated, high-risk population. Bladder recurrence-free survival (RFS) was analyzed as the primary end point; based on data collected during a median follow-up of 22.9 months after the start of induction therapy, the rate was 60% at 1 year and 46% at 2 years.

Findings from secondary end point analyses showed the rate of high-grade RFS was 65% at 1 year and 52% at 2 years. The progression-free survival rate was 97% at 1 year and 93% at 2 years.

Urgency/frequency and dysuria were the most common adverse effects (AEs) of the instillations. Fifty-nine percent of patients experienced no AEs, just 3% were unable to complete full induction therapy, and there were no treatment-related deaths, reported Nathan A. Brooks, MD, urologic oncology fellow at The University of Texas MD Anderson Cancer Center in Houston.

“There is an unmet need for alternatives to radical cystectomy for patients with high-risk NMIBC that recurs after BCG,” Brooks said.

“[Using] intravesical gemcitabine and docetaxel avoids systemic infusion and has other advantages [because] both medications are generic, [are] easily reconstituted, and have not been plagued by supply shortages. Based on these features and our study’s findings, we believe that prospective evaluation of intravesical gemcitabine/docetaxel is not only warranted but is pragmatically necessary for patients with BCG failure and possibly for BCG-naïve patients, given the current and recurrent supply shortages for BCG,” added Brooks, who worked on the study with Michael O’Donnell, MD, and co-authors.

The nationwide study identified patients treated at 9 centers between June 2009 and May 2018 for recurrent NMIBC after prior BCG. Eligible patients also needed to have completed at least 1 surveillance follow-up visit.

The intravesical regimen involved 6 weekly instillations of gemcitabine 1 g/50 mL sterile water that was drained after 60 to 90 minutes and followed by docetaxel 37.5 mg/50 mL with a dwell time of 90 to 120 minutes. Some patients received oral sodium bicarbonate the night before and the morning of the treatment, as well as prophylactic oral ondansetron. Most patients who had no recurrence at 3 months went on to receive 12 to 24 monthly maintenance instillations, although some received 3 weekly minicourses of treatment at 3 months, at 6 months, and every 6 months from induction. At 1 institution, the chemotherapy was heated prior to instillation.

No difference in outcomes across institutions

“Although there was some heterogeneity in the treatment regimens used, we observed no differences in outcomes in analyses of individual institutions,” Brooks said.

The study patients had received 1 to 8 prior courses of BCG with a median of 2 prior courses; 38% were unresponsive to BCG, and 61% were judged to be candidates for cystectomy by their treating physicians. Carcinoma in situ was present in almost two-thirds of patients, and approximately 90% had high-grade disease.

Median time to recurrence for those who recurred was 6.8 months. BCG failure category (relapsing, intolerant, unspecified, unresponsive) and pathologic subgroup were not associated with response to gemcitabine/docetaxel, Brooks reported.

Among patients without recurrence at 4 months, receipt of maintenance intravesical therapy was associated with improved bladder RFS. The bladder cancer-specific mortality rate for the cohort was 1% in the first year and 4% in the second year.

“These low mortality rates suggest there is a safe window for potential curative cystectomy,” Brooks said.

He noted that the retrospective design is a limitation of the study: “[Although] our review lacks the specific entrance criteria of prospective studies, it is strengthened by its large sample size, multi-institutional nature, and 2-year results.”

References

1. Brooks N, Steinberg R, Thomas L, et al. A multi-institutional evaluation of rescue therapy with intravesical gemcitabine and docetaxel for non-muscle invasive bladder cancer after BCG failure. Paper presented at: 2020 American Urological Association Virtual Experience; June 27-28, 2020.

2. Steinberg R, Thomas L, Brooks N, et al. Multi-institution evaluation of sequential gemcitabine and docetaxel as rescue therapy for nonmuscle invasive bladder cancer. J Urol. 2020;203(5):902-909. doi:10.1097/JU.0000000000000688