Use of intracavitary lnterferon-alpha-2b in the prophylactic treatment of patients with superficial bladder cancer

Abstract

The evolution of superficial transitional cell carcinoma (TCC) of the bladder poses a clinical management problem due to its tendency to recur after initial transurethral resection (TUR). Natural Killer (NK) cells are a distinct subset of lymphocytes that possess the ability to lyse tumor cells without prior sensitization in a nonmajor histocompatibility-restricted fashion. These cytotoxic cells constitute a relevant barrier against the local growth and systemic dissemination of neoplastic diseases. The immunomodulatory effect, after TUR of the tumor, of the prophylactic treatment with intravesical instillations of interferon-alpha-2b (IFN-alpha-2b) upon the NK activity of peripheral blood mononuclear cells (PBMNC) in 17 patients with superficial TCC of the bladder was analyzed using a 4-hour 51sodium chromate (51Cr)-release cytotoxicity assay against both NK-sensitive, or K562, and NK-resistant, or JY, tumor target cells. There were no significant modifications of the NK activity of PBMNC during the 3 months of IFN-alpha-2b intracavitary treatment (P > 0.05). However, with respect to their levels before treatment, NK activity in PBMNC at 3 months posttreatment was enhanced significantly in the 14 patients who showed no sign of tumor recurrence in the 12 months of follow-up (P < 0.01). Six months after finishing the intracavitary IFN-alpha-2b instillations, the PBMNC NK activity in these patients had returned to the levels found before initiating the therapy (P > 0.05). This temporary enhancement of the PBMNC NK activity was not found in three patients with evidence of tumor recurrence at some time during the 12 months after treatment. In similar experimental conditions, significant enhancement of the NK activity in PBMNC was not observed in nine patients with superficial bladder TCC who were treated with intracavitary instillations of mitomycin C (MMC) after the TUR of the tumor and who were free of recurrence of the disease at 1 year of follow up. The prophylactic intracavitary treatment of superficial bladder TCC with IFN-alpha-2b may induce an immunomodulatory effect in the NK activity of PBMNC that appears to be associated with the clinical evolution of the disease.