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Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.

Publication ,  Journal Article
Tan, WP; Chang, A; Brousell, SC; Grimberg, DC; Fantony, JJ; Longo, TA; Etienne, W; Spasojevic, I; Maccarini, P; Inman, BA
Published in: Int J Hyperthermia
2020

BACKGROUND: Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. OBJECTIVE: To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). METHODS: Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. RESULTS: The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. CONCLUSIONS: Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.

Duke Scholars

Published In

Int J Hyperthermia

DOI

EISSN

1464-5157

Publication Date

2020

Volume

37

Issue

1

Start / End Page

854 / 860

Location

England

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Swine
  • Oncology & Carcinogenesis
  • Mitomycin
  • Hyperthermia, Induced
  • Hyperthermia
  • Female
  • Antibiotics, Antineoplastic
  • Animals
  • Administration, Intravesical
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tan, W. P., Chang, A., Brousell, S. C., Grimberg, D. C., Fantony, J. J., Longo, T. A., … Inman, B. A. (2020). Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study. Int J Hyperthermia, 37(1), 854–860. https://doi.org/10.1080/02656736.2020.1780328
Tan, Wei Phin, Andrew Chang, Steven C. Brousell, Dominic C. Grimberg, Joseph J. Fantony, Thomas A. Longo, Wiguins Etienne, Ivan Spasojevic, Paolo Maccarini, and Brant A. Inman. “Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.Int J Hyperthermia 37, no. 1 (2020): 854–60. https://doi.org/10.1080/02656736.2020.1780328.
Tan WP, Chang A, Brousell SC, Grimberg DC, Fantony JJ, Longo TA, et al. Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study. Int J Hyperthermia. 2020;37(1):854–60.
Tan, Wei Phin, et al. “Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.Int J Hyperthermia, vol. 37, no. 1, 2020, pp. 854–60. Pubmed, doi:10.1080/02656736.2020.1780328.
Tan WP, Chang A, Brousell SC, Grimberg DC, Fantony JJ, Longo TA, Etienne W, Spasojevic I, Maccarini P, Inman BA. Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study. Int J Hyperthermia. 2020;37(1):854–860.

Published In

Int J Hyperthermia

DOI

EISSN

1464-5157

Publication Date

2020

Volume

37

Issue

1

Start / End Page

854 / 860

Location

England

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Swine
  • Oncology & Carcinogenesis
  • Mitomycin
  • Hyperthermia, Induced
  • Hyperthermia
  • Female
  • Antibiotics, Antineoplastic
  • Animals
  • Administration, Intravesical