A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer.

This study was designed to evaluate the efficacy and toxicity of the immunotoxin N901-blocked ricin (bR) in patients with small-cell lung cancer (SCLC) who achieved a complete or near-complete response following chemotherapy and/or radiation. Treatment consisted of a 7-day continuous infusion of N901-bR at a dose of 30 mg/kg/day followed by patient evaluation with repeat scans. Serum immunotoxin levels, human antimurine antibodies, and antiricin antibodies were determined during the course of the infusion. Nine patients enrolled in the study before it closed following a treatment-related death. Seven patients had extensive-stage disease and entered the study with a more than 90% reduction of their original tumor. Two patients with limited-stage SCLC had no evidence of disease at study entry. Maximum plasma levels of N901-bR ranged from 72-371 ng/mL. Laboratory toxicity consisted of transient transaminitis in 8 patients and creatine kinase elevation in 3 patients, 1 of whom developed premature ventricular contractions. One patient experienced progressive capillary leak syndrome following immunotoxin infusion, which proved fatal. All patients developed antibodies to the infused murine antibody as well as to the toxin. Six patients died of progressive SCLC and 1 patient died of presumed radiation pneumonitis. One patient with limited-stage disease is still alive more than 6 years after therapy. N901-bR therapy was associated with a fatal incident of capillary leak syndrome and a nearly universal development of human antimouse and antiricin antibodies, which limited its further clinical development.