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 approximately 50% of breast carcinomas, was given by continuous iv infusion at a dose of 50 micrograms/kg per day or 100 micrograms/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.
Gould
B J
BJ
Department of Hematology/Oncology, Duke University Medical Center, Durham, N.C. 27710.
Borowitz
M J
MJ
Groves
E S
ES
Carter
P W
PW
Anthony
D
D
Weiner
L M
LM
Frankel
A E
AE
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D004341:Drug Evaluation; D004487:Edema / Q000209:etiology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology; D011654:Pulmonary Edema / Q000209:etiology; D012276:Ricin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012276:Ricin