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.