Quadruple immunotherapy of Bacillus Calmette-Guérin, interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor as salvage therapy for non–muscle-invasive bladder cancer

Ryan L. Steinberg, Kenneth G. Nepple, Kyla N. Velaer, Lewis J. Thomas, Michael A. O'Donnell

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non–muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal. Objective We hypothesized that further immunostimulation with intravesical interleukin-2 and subcutaneous granulocyte-macrophage colony-stimulating factor may improve response to intravesical BCG and IFN in patient with prior BCG failure(s). Methods A retrospective review was performed. Patients received 6 treatments of quadruple immunotherapy (intravesical solution with one-third dose BCG, 50 million units IFN, and 22 million units interleukin-2, along with a 250-mcg subcutaneous sargramostim injection). Surveillance began 4 to 6 weeks after treatment completion. Patients received maintenance if recurrence-free. Success was defined as no recurrence (bladder or extravesical) and bladder preservation. Analysis was performed by Kaplan-Meier method (P<0.05). Results Fifty-two patients received treatment with a median recurrence follow-up of 16.3 months and overall follow-up of 41.8 months. All patients had at least 1 prior BCG failure and 13% had 2 or more prior failures. Only 3 patients (6%) were unable to tolerate full induction. Treatment success was 55% at 1 year, and 53% at 2 years. Thirteen patients (25%) underwent cystectomy at a median time of 17.3 months with disease progression to T2 in 1 patient and T3 in 2 patients. No patients had positive surgical margins or positive lymph nodes. Conclusions In patients with non–muscle-invasive bladder cancer with prior BCG failure, quadruple immunotherapy demonstrated good treatment success in some patients and warrants further evaluation.

Original languageEnglish
Pages (from-to)670.e7-670.e14
JournalUrologic Oncology: Seminars and Original Investigations
Volume35
Issue number12
DOIs
StatePublished - Dec 2017

Keywords

  • Administration, intravesical drug
  • Granulocyte-macrophage colony-stimulating factor
  • Immunotherapy
  • Interferons
  • Interleukin-2
  • Mycobacterium bovis
  • Urinary bladder neoplasms

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