e16048 Background: Intravesical BCG (Bacillus Calmette-Guérin) is the gold standard for treatment of superficial bladder cancer. Recurrence is a significant problem. Intravesical interferon α (IFN) demonstrated complete response (CR) in ∼40% patients with most relapsing <1 year. Intravesical Ad-IFN takes advantage of the bladder to allow prolonged exposure to high concentrations of IFN; this is expected to potentiate durable therapeutic responses. Syn3 is an excipient used to increase adenoviral vector (Ad) transfection. Methods: The phase I study is a nonrandomized, open-label, rising-dose, multi-center study of Ad-IFN in patients with papillary bladder cancer, or carcinoma in situ refractory to BCG. Patients with T1 were not enrolled unless they refused cystectomy. A minimum of 3 subjects were enrolled at each dose level. Adverse events and lab abnormalities were graded according to CTC version 3 criteria. The occurrence of treatment-related Grade 3 or Grade 4 toxicity is considered dose-limiting toxicity (DLT). The maximum tolerated dose is defined as the dose which results in DLT in ≤1/6 subjects. Urine from pre-treatment, posttreatment days 0–7, 10, 14, and 28 were tested for IFN, Syn3, Ad-IFN DNA, and research biomarkers. Blood was assayed for IFN, Syn3, Ad-IFN DNA, anti- adenovirus and anti-IFN antibodies. Results: Intravesical administration of 3×109, 1×1010, 3x1010, 1×1011, or 3×1011 particles/ml of Ad-IFN (75ml) in 1mg/ml Syn3 is safe with only minor initial urgency controlled with anticholinergic medication. Of the 13 evaluable patients, 6 are CR, defined as a negative cytology and biopsy at 3 months. CR patients were offered a second dose. Response duration is variable with longest >1 year. Urinary IFN was seen for all patients in a dose-dependent fashion. TRAIL, IP-10, M65, and M30 were also seen. Conclusions: Initial safety and response activity justify further clinical development. [Table: see text]
A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part II: Immunological aspects