Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin's disease.

The objective of this study was to determine the therapeutic ratio of fractionated radiolabeled immunoglobulin therapy (RIT) for patients with recurrent Hodgkin's disease. Ninety patients with recurrent Hodgkin's disease received 2 mg of yttrium-90-labeled polyclonal rabbit antihuman ferritin IgG i.v. Fifty-seven patients received a single (unfractionated) administration per treatment cycle; 11 of them were treated with 0.3 mCi/kg body weight, 39 were treated with 0.4 mCi/kg body weight, and 7 received 0.5 mCi/kg body weight per treatment cycle. Thirty-three patients had their radiolabeled immunoglobulin administration separated (fractionated) in 2 x 0.25 mCi/kg body weight (total activity, 0.5 mCi/kg). The interval between fractions was 1 week. Radioimmunoconjugates did not cause serious acute side effects. In vivo radioimmunoconjugates were stable. Human antirabbit IgG antibodies were found in 2 of 50 retreated patients (<5%). Hematological toxicity was the only side effect noted in all patients, and it was usually temporary. Response rates (RRs) were 20%, 61%, and 86% after 0.3, 0.4, or 0.5 mCi/kg unfractionated yttrium-90-labeled antiferritin. The RR for patients treated with fractionated RIT was 42%. In the fractionated RIT group, complete responses were decreased, and progressive disease increased (P < 0.05). Complete responses had a medium duration of 6 months. Median survival times were 390 days for 1 x 0.4 mCi/kg and 300 days for the 2 x 0.25 mCi/kg patient group. Fractionation did not provide the expected decrease in hematological toxicity or the expected increase in tumor RRs.

Recurrence of Hodgkin's disease after indium-111 and yttrium-90 labeled antiferritin administration.

BACKGROUND: Indium-111 labeled antiferritin targets 95% of all Hodgkin's disease lesions with a diameter of 1 cm or more. Subsequent treatment with yttrium-90 labeled antiferritin secures a high response rate in patients with recurrent Hodgkin's disease. METHODS: A total of 87 patients were entered on one of three different yttrium-90 labeled antiferritin protocols. Recurrences after yttrium-90 treatment were analyzed. Nine patients were retreated with involved external beam radiation fields, selected with the help of indium-111 labeled antiferritin. RESULTS: In single-agent yttrium-90 antiferritin studies, a response rate of more than 60% was found, with an average response duration of 6 months. One-third of the patients had recurrences in previously uninvolved areas. Repeat indium antiferritin scintigraphy allowed for the selection of new radiation fields for recurrences. In-field disease control was obtained for a median of 8 months, but new recurrences in new areas occurred. Chemotherapy or radiation therapy given immediately before antiferritin decreased tumor targeting with indium-111 labeled antiferritin. CONCLUSIONS: Recurrences after radiolabeled antiferritin treatment are not due to radioresistant Hodgkin's disease. In contrast, Hodgkin's disease less than 1 cm in diameter is not targeted and not controlled by radiolabeled antiferritin. New multimodality regimens with a higher therapeutic ratio are needed for treatment of Hodgkin's disease with curative intent. Radiolabeled antiferritin can be incorporated in such regimens to secure better control of bulky Hodgkin's disease (>1 cm in diameter), but it should be given before chemotherapy or radiation therapy.