A Randomized Controlled Study of Intravesical α−2b-Interferon in Carcinoma in Situ of the Bladder

Abstract

We treated 87 patients with carcinoma in situ of the bladder in a prospective randomized trial of 2 dose levels of intravesically administered alpha-2b-interferon. Patients received either low dose (10 million units) or high dose (100 million units) recombinant alpha-2b-interferon weekly for 12 weeks and then monthly for a maximum of 1 year. Of the 47 high and 38 low dose patients 20 (43%) and 2 (5%), respectively, achieved a complete response. Additionally, partial responses (cytology results positive with no histological evidence of carcinoma in situ) were noted in 23% of the high dose group. Notably, 6 of 9 patients who had failed prior intravesical bacillus Calmette-Guerin therapy responded to alpha-2b-interferon treatment. Preliminary assessment has shown that among the complete responders 18 of 20 (90%) in the high dose group have maintained responses for at least 6 months after the completion of treatment (10 for more than 12 months). Seven patients in each treatment group have undergone radical cystectomy. All 14 patients had progressive disease except 1 who chose cystectomy although she was still responding to treatment. The median intervals from initial treatment to cystectomy were 18 and 32 weeks in the low and high dose groups, respectively. Local irritation or toxicity did not occur and other adverse effects were rare except for mild to moderate flu-like symptoms (8% in the low dose and 17% in the high dose groups). No patient discontinued therapy due to treatment-related adverse effects. Intravesical alpha-2b-interferon demonstrated a high level of activity in the treatment of carcinoma in situ of the bladder with the 100 million unit dose producing a significantly greater response rate (43% complete response, p less than 0.0001) than the low dose (5% complete response). Safety and tolerance were excellent with no local irritative toxicity.

Adenoviral Mediated Interferon-α 2b Gene Therapy Suppresses the Pro-Angiogenic Effect of Vascular Endothelial Growth Factor in Superficial Bladder Cancer

“…14 IFN-␣ 2b is well tolerated as monotherapy for superficial bladder cancer and it has shown some dose related clinical efficacy after BCG failure, although the durability of the response is limited. 5 Recently IFN-␣ 2b was combined with BCG in an attempt to enhance the cellular immune response to BCG and improve the response. 12 The combination was effective in some patients with BCG refractory disease but many with an initial response later experienced relapse and ultimately required cystectomy.…”

“…4 Unfortunately treatment of superficial bladder cancer with intravesical IFN-␣ protein has yielded a complete response rate of less than 20% to date, possibly because therapeutic levels of IFN-␣ protein are not sustained in urine and tissue after bolus administration. 5 Inhibition of tumor growth and angiogenesis through gene therapy using an adequate and prolonged dose of immunomodulators such as IFN-␣ 2b represents an attractive and promising approach to overcome the limitations of IFN-␣ protein therapy for superficial disease. The bladder is an optimal site for evaluating gene therapy because the vector containing the transgene can be instilled directly into the bladder and it establishes direct contact with the tumor, which should enhance gene transfer.…”

Optimal Treatment of Non-Muscle Invasive Urothelial Carcinoma Including Perioperative Management Revisited

“…IFN-α 2b as a single intravesical agent has shown shortterm efficacy but demonstrated recurrence rates similar to placebo on long-term follow-up [41,42]. In a randomized controlled trial the combination of BCG plus IFN showed results similar to BCG alone [43].…”

Immunotherapy for bladder cancer

“…These responses were achieved with minimal local and systemic toxicity. Glashan [55] treated 87 patients with CIS in a prospective randomized trial who received either low-dose (10 MU) or high-dose (100 MU) recombinant INF alpha-2b weekly for 12 weeks and then monthly for a maximum of 1 year. The study found that tumor response to IFN was dose dependent, with 5% CR and 32% PR observed with a dose of 10 MU and 43% CR and 19% PR observed with a dose of 100 MU.…”