A phase I trial for the use of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) in the treatment of BCG-refractory nonmuscle invasive urothelial carcinoma of the bladder.

Abstract

313 Background: Salvage intravesical chemotherapy has shown benefit in patients with high-risk non-muscle invasive bladder cancer who fail first line therapy. Our preclinical murine intravesical trial showed a combination therapy was superior to single-agents. Our objective was to investigate the safety of intravesical triple agent salvage chemotherapy consisting of cabazitaxel, gemcitabine and cisplatin (CGC). Methods: Patients with BCG refractory or recurrent high-risk non-muscle invasive bladder cancer who refused radical cystectomy were enrolled. All patients underwent a pre-treatment transurethral resection of bladder tumor and then received a 6-week regimen. All patients received the same dose of gemcitabine (2000mg) while the dose of cisplatin and cabazitaxel were escalated as shown in table 1. Toxicity was categorized according to CTC for Adverse Events v4 and included hematuria, dysuria, bladder spasm, urinary retention or frequency. A complete response (CR) was defined as a negative random bladder biopsy and negative cytology six weeks after treatment. Results: Median age of the 9 patients was 74 years (table 1) and the median number of prior intravesical therapies was 4 (range 2-5). All patients completed 6 weeks of induction CGC. Any local toxicity was found in 7 patients with 5 experiencing at least 1 grade 1 toxicity and 4 experiencing at least 1 grade 2 toxicity. Seven of eight patients were complete responders and initiated maintenance therapy. Conclusions: CGC appears to be a well-tolerated intravesical salvage chemotherapy regimen for the treatment of BCG-refractory NMIBC. Clinical trial information: NCT02202772. [Table: see text]

Hyperthermia Improves Solubility of Intravesical Chemotherapeutic Agents

“…The initial concentration ranges studied for each drug were based on standard intravesical administration doses -mitomycin C 1.0-2.0 mg/mL, gemcitabine 20-40 mg/mL, and cisplatin 0.6-1.0 mg/mL [24][25][26][27][28][29][30][31][32]. For gemcitabine and cisplatin, when standard doses were shown to be easily soluble with hyperthermia, upper limits were increased to 80 and 3.5 mg/mL respectively to identify the heated kinetic solubility points.…”

Intravesical Therapy – BCG and Beyond

“…DeCastro et al reported the results of a Phase I trial in a cohort of 9 patients with prior BCG failure and a median of 4 prior intravesical therapies [32]. Treatment included 2000 mg of gemcitabine and an escalating dose of cabazitaxel alone (first 4 patients), then gemcitabine, cabazitaxel (5 mg) and an escalating dose of cisplatin (next 5 patients).…”

New therapies in nonmuscle invasive bladder cancer treatment

“…Early results show that intravesical CGC appears to be well tolerated in patients with NMIBC, with five patients experiencing at least one Grade 1 toxicity and the remaining four patients experiencing at least one Grade 2 toxicity. [ 51 ]…”