title: Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.
abstract: To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.
authors.affiliation: Division of Medical Oncology, University of Colorado Cancer Center, Denver 80262.
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez
authors.forename: P
authors.initials: P
authors.lastname: Salem
authors.forename: P A
authors.initials: PA
authors.lastname: Bunn
authors.forename: A A
authors.initials: AA
authors.lastname: Zukiwski
authors.forename: R
authors.initials: R
authors.lastname: Lamb
authors.forename: R S
authors.initials: RS
authors.lastname: Benjamin
authors.forename: L
authors.initials: L
authors.lastname: Spitler
authors.forename: N
authors.initials: N
authors.lastname: Wedel
authors.forename: W A
authors.initials: WA
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008875:Middle Aged; D012276:Ricin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012276:Ricin