Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

Abstract

Non-muscle-invasive bladder cancer is a challenging disease, even given its superficial nature. It is prone to multiple recurrences and progression to muscle-invasive cancer. These features of this disease contribute significantly to reduced quality of life as well as creating significant morbidity and even mortality. Randomised trials demonstrate that when hyperthermia is added to conventional mitomycin-C treatment that local control rates and progression-free survival are substantially improved. In this review we consider how hyperthermia can exert such beneficial effects. Some of the mechanisms presented are theoretical, while others are facts. It is hoped that this review will contribute rationale for further examination of mechanisms, because an understanding of such mechanisms may lead to even better chemotherapeutic approaches, as well as potential biomarkers for predicting and monitoring treatment success.ARTICLE HISTORY

Bladder intracavitary hyperthermic perfusion chemotherapy for the prevention of recurrence of non-muscle invasive bladder cancer after transurethral resection

“…In the present study, both BHPC and intravesical chemotherapy achieved high local drug concentrations in the perfusion liquid, thus, at the intravesical cavity of the bladder, but serum concentrations of MMC were maintained below those associated with systematic administration of the drug. Although, the serum MMC concentrations in the BHPC group were significantly higher than those in the intravesical perfusion chemotherapy group in the present study, it did not reach sufficiently high levels to cause serious adverse effects (21,34,35). The advantages of BHPC over single intravesical chemotherapy can be attributed to the synergy of local hyperthermia treatment and chemotherapy.…”

“…This result suggested that bladder mucosal wound by TUR of bladder carcinoma did not increase the absorption of chemotherapeutic drugs. In addition, the plasma half-life of MMC is 30-50 min (34,35), and we found that the serum MMC concentration remained stable during BHPC, but rapidly declined after BHPC. We hypothesized that absorption of chemotherapeutic drugs compensated for metabolism of chemotherapeutic drugs during BHPC The aim of BHPC treatment post-TUR is to cause maximal killing of residual tumors, with minimal damage to normal tissues.…”

Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons

“…88 Activation of cell death pathways, direct damage to proteins responsible for drug resistance, and enhanced drug delivery are the most important mechanisms by which PDT mediates the reversing of MDR. 89…”

Clinical validation of a novel thermophysical bladder model designed to improve the accuracy of hyperthermia treatment planning in the pelvic region

“…The dynamic model presented in this article significantly improves temperature predictions of bladder (wall) temperatures, which provides opportunities for further clinically related research and improvement of quality assurance. As temperature is correlated to penetration depth of the chemotherapeutic instillation [50], future research will include a study of the relation between hyperthermic dose and clinical effect, taking into particular account the relation between temperatures measured in the bladder, the computed temperature in the bladder wall, and the therapeutic benefit.…”