Development and investigation of a novel device with gemcitabine for hyperthermic intravesical chemotherapy

Abstract

Purpose

To evaluate the safety and efficacy of a novel hyperthermic intravesical chemotherapy (HIVEC) device in combination with gemcitabine.

Materials and methods

A pilot clinical trial was performed on patients with high-risk non-muscle invasive bladder cancer (NMIBC), who received HIVEC via the novel device (BR-PRG). Treatment regimen included eight weekly instillations of intravesical GEM (3 g in 150 mL normal saline [NS]) at a temperature of 45 °C for 60 min. Assessment of adverse events (AEs) was the primary objective of the trial. Disease recurrence and the thermal stability of GEM were also analyzed.

Results

A total of 116 HIVEC treatments were delivered. Fifteen and eighteen patients were included in the effectiveness and safety analysis, respectively. Median follow-up was 12 months; five patients experienced a disease recurrence. One-year cumulative incidence of recurrence was 23.8% in EORTC intermediate risk group and 37.5% in high-risk group. Ten patients experienced at least one AE, with the most common being acute urinary tract infection, followed by urinary tract pain, and hematuria. Two patients experienced acute cystitis (grade 3 AE) and instillations were postponed until full recovery. Other AEs were minor, and no systemic toxicity was observed. The contents of GEM in solution of 0.9% NS or NS mixed with artificial urine were stable at 25 °C, 37 °C, 43 °C, 45 °C, 47 °C and 50 °C for 2 h.

Conclusion

GEM can be an ideal drug for use in HIVEC due to its good thermal stability. BR-PRG, combined with GEM was safe and effective in administering HIVEC.

Keywords:

• Bladder cancer
• hyperthermia
• intravesical chemotherapy
• gemcitabine
• recurrence

Disclosure statement

Bright Medical provided the BR-PRG device and disposable perfusion pipe used in this study free of charge but had no participation in data analysis, manuscript preparation, or manuscript approval. The authors alone were responsible for the content and writing of the manuscript.

Additional information

Funding

This work was supported by the Guangzhou Clinical Characteristic Technology Project under Grant [number 2019TS40]; Clinical Research 5555 Project of Affiliated Cancer Hospital and Institute of Guangzhou Medical University under Grant [number IIT-2021-003(MN1)].