Phase I study of an anti-breast cancer immunotoxin by continuous infusion: Report of a targeted toxic effect not predicted by animal studies

260F9 Monoclonal antibody-recombinant ricin A chain, an immunotoxin reactive with ≈50% of breast carcinomas, was given by continuous iv infusion at a dose of 50 μg/kg per day or 100 μg/kg per day. Five patients with refractory breast cancer received treatment for from 6 to 8 days. Severe toxic effects, including marked fluid overload and debilitating sensorimotor neuropathies, occurred in most patients. Immunoperoxidase studies suggested that 260F9 monoclonal antibody targeting of the Schwann cells may have induced demyelination and subsequent neuropathy. This is the first report of a targeted toxic effect due to an immunoconjugate.