e15560 Background: Patients with non-muscle-invasive bladder cancer (NMIBC) that fail intravesical bacillus Calmette-Guérin (BCG) are at high risk for progression. Radical cystectomy is an effective but morbid treatment option. We tested the safety and efficacy of combined intravesical mitomycin C (MMC) and external deep regional hyperthermia (HT) as a bladder-sparing approach for BCG-refractory NMIBC. Methods: Patients with BCG-refractory NMIBC were eligible for this phase I clinical trial. Treatment consisted of intravesical MMC (40 mg in 40 mL) with concurrent HT with target temperature of 42°C. MMC dwell time was 60-120 min and heating time was 40-60 min. HT was delivered using a BSD2000 device and temperatures monitored with skin, bladder and rectal probes. Treatment was given weekly for 6 weeks (induction) then monthly for 4 months (maintenance). The primary endpoint was toxicity which was assessed using CTCAE 3.0. Secondary endpoints included recurrence-free survival (RFS), progression-free survival (PFS), cystectomy, and overall survival (OS) which were assessed at 3 month intervals with cystoscopy and cytology for 2 years. Results: Fifteen patients were eligible and consented to the clinical trial. Median age was 66 years and 87% were male. Median follow-up was 2.85 years. One patient did not tolerate supine position, two completed induction but recurred prior to maintenance, one recurred after 3 maintenance treatments, and 11 patients received all 10 treatments. The 2 year RFS was 33% (median RFS = 15.4 mos). Six patients (40%) required cystectomy (median time = 20.1 mos). No patient had bladder progression but two patients developed ureteral tumors (not present on baseline imaging). Two patients died, one from ureteral cancer and one of cardiovascular disease, for a 3-year OS of 83% (median OS not reached). No grade III toxicities were observed. Common toxicities were abdominal pain (36%), cystitis (22%), pruritis and urinary tract infection (14%). Conclusions: The combination of MMC and HT for BCG refractory NMIBC was safe and associated with low grade toxicity. While recurrence was common, progression did not occur, and recurrent patients were safely salvaged with cystectomy. Clinical trial information: NCT00734994.
OS6.4 NOA-16: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group evaluating a mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas
