Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin.
We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012276:Ricin / Q000627:therapeutic use*; D012709:Serum Albumin / Q000032:analysis
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000922:Immunotoxins; D012709:Serum Albumin; C059257:XomaZyme; D012276:Ricin