Iodine 131 antiferritin, a new treatment modality in hepatoma: a Radiation Therapy Oncology Group study.
One hundred five patients with hepatoma were treated with iodine 131 antiferritin in three sequential protocols in phase 1-2 trials. Therapy began in all trials with external beam irradiation and chemotherapy. The dosimetric results with 131I antiferritin indicated that 30 mCi (8 to 10 mCi/mg immunoglobulin G [IgG]) was sufficient to saturate the tumor. Tumor-effective half-life of the radioactive antibody was 3 to 5 days and was dependent on the species of animal from which the antibody was derived. This led to a 30 mCi on day 0 and 20 mCi on day 5 treatment schedule. Toxicity was predominantly thrombocytopenia. Due to clinical remission, cyclic therapy was next developed with antibodies from different species of animals. Rabbit, pig, monkey, and bovine antibodies were determined to produce the longest tumor-effective half-life and therefore the highest dose of radiation. Integration of 15 mg doxorubicin and 500 mg 5-fluorouracil (5-FU) with 131I antiferritin was accomplished next. Remission to external beam radiation was evaluated by computed tomography (CT) scan tumor volume computations that indicated that 22% of the patients had a partial remission (PR) from initial presentation to 1 month following external irradiation and chemotherapy. From the time of radioactive antibody administration, 48% of the patients (7% complete response [CR] and 41% PR) achieved remission to 131I antiferritin. Of 79 patients evaluated by CT scan tumor volumetrics 50% of the patients (7% CR and 43% PR) remitted to the entire treatment regimen. Patients not previously treated and without metastasis who were alpha fetoprotein positive (AFP+) had a 5-month median survival compared with AFP- median survival of 10 1/2 months. There were four CRs with one being 3 years and 6 months. The longest PR was 5 years and 8 months. These studies have demonstrated the toxicity and therapeutic activity of 131I antiferritin and the emerging role of radiolabelled antibody in cancer therapy.
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Stillwagon
J L
JL
Klein
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Leichner
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Siegelman
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Fishman
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Ettinger
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T
Haulk
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K
Kopher
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Finney
D000293:Adolescent; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D005293:Ferritins / Q000276:immunology*; D006207:Half-Life; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014055:Tomography, Emission-Computed; D014057:Tomography, X-Ray Computed; D000509:alpha-Fetoproteins / Q000032:analysis
D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D000509:alpha-Fetoproteins; D005293:Ferritins