Combined Low-Dose Intravesical Immunotherapy (BCG + Interferon a-2b) in the Management of Superficial Transitional Cell Carcinoma of the Urinary Bladder: A Five-Year Follow-Up

Abstract

Between July 1994 and July 2001, all patients with superficial transitional cell carcinoma (TCC) of urinary bladder (pT1 and pTa), 7 days after undergoing transurethral resection of tumor were subjected to intravesical instillation of 60 mg BCG (Danish 1331) combined with 5 million IU interferon alpha-2b (Intron-A) mixed with 50 ml of physiological saline weekly for 8 weeks, then fortnightly for 8 weeks, then monthly for 8 weeks, followed by maintenance dose at the end of the 9th, 12th, 18th, 24th months. Each instillation was for 2 h duration with an average follow-up period of 60 months. At the end of the 1st year of follow-up 84% of patients had no tumor recurrence which dropped to 36% at the end of 5-year follow-up, while no incidence of disease progression at the end of the first year was recorded but was 20% at the end of 5 years, thereby resulting in a disease progression-free 5-year interval in 80% of our patients. Drug tolerance was excellent with a very low incidence of toxicity.

Antitumor effects of human interferon-alpha 2b secreted by recombinant bacillus Calmette-Guérin vaccine on bladder cancer cells

“…Cytokines such as interleukin-2 (IL-2), interferon (IFN), and tumor necrosis factor-alpha (TNF-α) are considered to play important roles in this process (Belldegrun et al, 1998;Mohanty et al, 2002;O′Donnell et al, 2004;Agarwal et al, 2010). It was expected that an increased local expression level of such molecules could enhance the antitumor effects of BCG.…”

“…To a certain extent, various studies in which BCG was combined with certain immunological molecules have supported this expectation. The combination of intravesical BCG and IL-2 or IFN treatment has shown better short-term effects on BTCC patients who initially did not respond well to BCG alone (Mohanty et al, 2002;O′Donnell et al, 2004). However, long-term effects were not improved.…”

“…However, long-term effects were not improved. On the other hand, treatment with exogenous cytokines has many unresolved problems such as high dosage, high frequency of side effects, short duration of drug activities, and high cost (Mohanty et al, 2002;O′Donnell et al, 2004). Recent research has focused more on exploring the function of BCG as a new vaccine vehicle, and on building recombinant BCG (rBCG) to increase its immunogenicity (Yamada et al, 2000;Arnold et al, 2004;Lee et al, 2004;Luo et al, 2004;Yu et al, 2007;Chade et al, 2008;Liu et al, 2009;Xu et al, 2009).…”

“…It acts directly on tumor cells to inhibit their proliferation and differentiation (Pfeffer et al, 1998;Zella et al, 1999;Moro et al, 2001). Data from large multicenter clinical trials have shown that BCG combined with IFNα-2b can enhance antitumor effects (Belldegrun et al, 1998;Mohanty et al, 2002;O′Donnell et al, 2004). However, this combination is not successful in eliminating negative aspects of the treatment such as the high dosage of IFNα-2b, the frequent occurrence of side effects, and the short duration of therapeutic effects.…”

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

“…[67][68][69][70] Longterm studies of up to 5 years show that, although early responses to the BCG-interferon treatment were excellent, 64% of patients had relapsed at 5 years with 20% having evidence of disease progression. 71 The combination of reduceddose BCG with IFNα has shown favourable longterm results in firsttime BCG failures. 70,72 By con trast, the only randomized study of the combination of BCG with IFNα2b in BCGnaive patients failed to demonstrate any superiority of the combination over BCG alone, even though the tolerability of reduced dose BCG-IFNα2b seemed to be better than that of fulldose BCG alone.…”