Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1a therapy in pancreatic carcinoma

Twenty-eight patients with unresectable, measurable pancreatic carcinoma and Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1 were treated with the murine monoclonal antibody 17-1 A, planning to administer 500 mg i.v. three times weekly for 8 weeks. Treatment was well tolerated, with an 18% incidence (five patients) of hypersensitivity reactions. All hypersensitivity episodes occurred in the first 3 weeks of therapy and required treatment discontinuation. Six patients required early discontinuation of therapy due to symptomatic progressive disease and one patient was removed from the study due to a protocol violation. Sixteen patients received the full course of 12 g of antibody. One patient has exhibited a durable partial response. Antibody pharmacokinetics were determined in five patients. In four patients peak 17-1A levels averaged 100 fig/ml with mean harmonic uh of 16.8 h in a one-compartment model. Neither pretreatment nor posttreatment levels of circulating 17-1A changed significantly during the 8 weeks of treatment, This study demonstrates the feasibility and acceptable toxicity of repetitive dosing with an unconjugated murine monoclonal antibody. The lack of efficacy of treatment suggests that factors other than prolonged exposure of tumor and cytotoxic effector cells to murine antibody are required for successful antibody therapy of pancreatic cancer.