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Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon-α and Interleukin-2 as Mono- or Combination-Therapy for Bladder Cancer in an Orthotopic Tumor Model:

Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon-α and Interleukin-2 as Mono- or... Objective To reduce adverse effects and improve efficacy of intravesical BCG for bladder cancer, alternative treatment options were investigated in an orthotopic rat tumor model. Methods Superficial bladder cancer was established in syngeneic female rat bladders by instillation of AY-27 cells. Animals were randomly assigned to treatment groups including dose escalation of intravesical BCG with or without interferon-α (IFN-α) or interleukin-2 (IL-2); or graded doses of gemcitabine alone; or BCG plus gemcitabine. Treatments were given twice weekly for 3 weeks. Rats in control groups received saline instillations. Treatment response was monitored by animals’ well-being, survival days, tumor growth inhibition, and histological examination at necropsy. Results Rats receiving monotherapy with intravesical BCG, gemcitabine, or IFN-α, attained significantly better survival and tumor reduction compared with control (P = 0.002; 0.001; 0.002, respectively, Log-rank Test). A dose-dependent treatment response was observed in animals with established bladder tumor receiving escalated BCG instillations. Only high-dose BCG significantly improved animal survival. Although high-dose BCG plus gemcitabine or IFN-α did not increase benefit over monotherapies, low-dose BCG plus IL-2 did show improved efficacy (P = 0.01). Conclusion Intravesical monotherapies with gemcitabine and IFN-α were as effective as BCG for treatment of early non-muscle-invasive urothelial bladder cancer in this immune competent rat model. Combining these agents with high-dose BCG did not further increase efficacy. However, combining low-dose BCG with IL-2 enhanced BCG effectiveness. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Medicine Insights: Oncology SAGE

Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon-α and Interleukin-2 as Mono- or Combination-Therapy for Bladder Cancer in an Orthotopic Tumor Model:

Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon-α and Interleukin-2 as Mono- or Combination-Therapy for Bladder Cancer in an Orthotopic Tumor Model:

Clinical Medicine Insights: Oncology , Volume 5: 1 – Sep 21, 2011

Abstract

Objective To reduce adverse effects and improve efficacy of intravesical BCG for bladder cancer, alternative treatment options were investigated in an orthotopic rat tumor model. Methods Superficial bladder cancer was established in syngeneic female rat bladders by instillation of AY-27 cells. Animals were randomly assigned to treatment groups including dose escalation of intravesical BCG with or without interferon-α (IFN-α) or interleukin-2 (IL-2); or graded doses of gemcitabine alone; or BCG plus gemcitabine. Treatments were given twice weekly for 3 weeks. Rats in control groups received saline instillations. Treatment response was monitored by animals’ well-being, survival days, tumor growth inhibition, and histological examination at necropsy. Results Rats receiving monotherapy with intravesical BCG, gemcitabine, or IFN-α, attained significantly better survival and tumor reduction compared with control (P = 0.002; 0.001; 0.002, respectively, Log-rank Test). A dose-dependent treatment response was observed in animals with established bladder tumor receiving escalated BCG instillations. Only high-dose BCG significantly improved animal survival. Although high-dose BCG plus gemcitabine or IFN-α did not increase benefit over monotherapies, low-dose BCG plus IL-2 did show improved efficacy (P = 0.01). Conclusion Intravesical monotherapies with gemcitabine and IFN-α were as effective as BCG for treatment of early non-muscle-invasive urothelial bladder cancer in this immune competent rat model. Combining these agents with high-dose BCG did not further increase efficacy. However, combining low-dose BCG with IL-2 enhanced BCG effectiveness.

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References (30)

Publisher
SAGE
Copyright
Copyright © 2022 by SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses
eISSN
1179-5549
DOI
10.4137/cmo.s7658
Publisher site
See Article on Publisher Site

Abstract

Objective To reduce adverse effects and improve efficacy of intravesical BCG for bladder cancer, alternative treatment options were investigated in an orthotopic rat tumor model. Methods Superficial bladder cancer was established in syngeneic female rat bladders by instillation of AY-27 cells. Animals were randomly assigned to treatment groups including dose escalation of intravesical BCG with or without interferon-α (IFN-α) or interleukin-2 (IL-2); or graded doses of gemcitabine alone; or BCG plus gemcitabine. Treatments were given twice weekly for 3 weeks. Rats in control groups received saline instillations. Treatment response was monitored by animals’ well-being, survival days, tumor growth inhibition, and histological examination at necropsy. Results Rats receiving monotherapy with intravesical BCG, gemcitabine, or IFN-α, attained significantly better survival and tumor reduction compared with control (P = 0.002; 0.001; 0.002, respectively, Log-rank Test). A dose-dependent treatment response was observed in animals with established bladder tumor receiving escalated BCG instillations. Only high-dose BCG significantly improved animal survival. Although high-dose BCG plus gemcitabine or IFN-α did not increase benefit over monotherapies, low-dose BCG plus IL-2 did show improved efficacy (P = 0.01). Conclusion Intravesical monotherapies with gemcitabine and IFN-α were as effective as BCG for treatment of early non-muscle-invasive urothelial bladder cancer in this immune competent rat model. Combining these agents with high-dose BCG did not further increase efficacy. However, combining low-dose BCG with IL-2 enhanced BCG effectiveness.

Journal

Clinical Medicine Insights: OncologySAGE

Published: Sep 21, 2011

Keywords: BCG; bladder cancer; gemcitabine; interferon-α; intravesical therapy

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