Washington, DC (UroToday.com) New treatment options for patients with BCG-refractory non-muscle invasive bladder cancer (NMIBC) are sorely needed. In this session, Dr. McKiernan commenced with a discussion of targeted therapies. Pre-clinically, murine models with inactivated PTEN and p53 demonstrate upregulation of the mTOR pathway. Such animals reliably form invasive bladder cancer. Inhibition of mTOR in these models reduced burden of disease. A phase 1 trial of nanoparticle albumin bound
(nab)-rapamycin has recently been completed and preliminary data were shared today. Thirteen eligible patients (BCG refractory with history of at least 2 prior induction therapies) received nab-rapamycin once weekly for 6 weeks. Despite measurable serum levels of rapamycin, there was no systemic toxicity and the urinary toxicity was less than BCG. The group at Memorial Sloan Kettering Cancer Center (MSKCC) is currently accruing a phase 1 trial of combination intravesical gemcitabine with systemic everolimus for 12 months. Results are eagerly awaited.
Dr. McKiernan referenced MSKCC medical oncologist Dean Bajorin who in 2006 asked him, “When are urologist going to learn that you can’t cure people with bladder cancer by putting one chemotherapy drug in their bladder for 6 cycles?” It appears that we are beginning to learn. Lightfoot and colleagues (Urol Oncol 2014) have demonstrated that treatment with sequential intravesical gemcitabine and mitomycin C resulted in a durable 38% 2-year recurrence free survival. At the SUO 2014 meeting, Steinberg and colleagues reported 34% CR at 2 years for patients undergoing combination gemcitabine and docetaxel in the BCG-refractory NMIBC setting. Dr. McKiernan’s group is currently accruing a phase 1 trial of combination intravesical cabazitaxel, gemcitabine, and cisplatin 3 days per week in a dose-escalation two-stage model for patients with BCG-refractory NMIBC.
The future of intravesical therapies for NMIBC may be in novel drug delivery mechanisms. Two examples, hyperbrached polyglycerol packaged taxanes and the TARIS drug delivery system, were described. These are currently in the preclinical testing arena.
In conclusion, preclinical models of bladder cancer exist. Intravesical mTOR targeting is feasible but may require drug combinations. Intravesical chemotherapeutic combinations are well tolerated and work. Novel drug delivery mechanisms are on the horizon and engender hope for better future treatment of patients with NMIBC.
James M. McKiernan, MD
Benjamin T. Ristau, MD. from the Society of Urologic Oncology Meeting - December 2 - 4, 2015 – Washington, DC.
Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA