Login to Access Video or Poster Abstract: MP15-18
Sources of Funding: Combat Medical

Introduction

The Combat BRS system is a novel hyperthermia delivering device which allows temperature controlled delivery and re-circulation of HM via a urethral catheter using an external heat source. HIVEC I and II are two randomized control trials to determine if HM is superior to MMC alone in intermediate risk non-muscle invasive bladder cancer (NMIBC). We report safety and tolerability outcomes comparing the two treatment arms.

Methods

HIVEC I and II are multi-centre, open-labeled randomized controlled trials recruiting patients from 25 Spanish and UK centers. The HIVEC I randomizes patients to either MMC, HM for 30 mins and HM for 60 mins (HM 60). Patients receive 4 once weekly treatments followed by 3 one monthly treatments. HIVEC II randomizes patients to MMC or HM 60 where both treatment arms receive 6 weekly treatments. Both trials use 40 mg MMC diluted in either 50 ml (HIVEC I) or 40 ml (HIVEC II) of sterile water. We compared all HIVEC I and II patients who were randomized to MMC (n=154) or HM 60 (n=153). _x000D_ _x000D_ HM was delivered by heating MMC to 43°C. Adverse events (AE) were reviewed by the independent data monitoring committee. HIVEC I and II were registered with EudraCT (2013-002628-18) and ISRCTN (23639415) respectively. _x000D_

Results

307 patients were included for analysis. 88.9% and 94.8% of HM and MMC patients respectively completed inductive therapy. Reasons for stopping therapy in 17 HM patients include: MMC allergy (n= 11), urinary symptoms (n=2), pain (n=1), haematuria (n=1), pneumonia (n=1) and in 8 MMC patients include: MMC allergy (n=7) and angina (n=1). AE which led to early termination of treatment were Grade II. There was no significant difference in patients with AE between HM (n=78, 51%) and MMC (n=66, 42.9%) (p=0.154). Most AE were Grade ?II (HM: 97.7%, MMC: 98.5%). There was no Grade >III related AE._x000D_ _x000D_ There was no difference in pain (HM: 13.1% vs MMC: 8.4, p=0.190), dysuria (HM: 5.2% vs MMC: 6.5%, p=0.617), urgency (HM: 11.8% vs MMC: 3.9%, p=0.067), incontinence (HM: 3.3% vs MMC: 0.6%, p=0.097) and rash/ allergic reaction (HM: 7.8% vs MMC: 5.2%, p=0.327). HM treated patients were significantly more likely to develop urinary frequency (HM: 15.0% vs MMC: 5.8%, p=0.008), haematuria (HM: 11.8% vs MMC: 3.9%, p=0.010) and bladder spasm (HM: 6.5% vs MMC: 0.6%, p=0.006). _x000D_

Conclusions

HM delivered using the Combat BRS system is safe and well tolerated. The majority of AE in the HM arm were low grade with urinary frequency and haematuria more common in HM in comparison to MMC treated patients. HM represents a safe and well tolerated intravesical treatment for NMIBC.

Funding

Combat Medical