PRINCETON, NJ--New approaches in radioimmunotherapy for patients with advanced breast cancer have had promising preliminary results, according to research presented at the Fifth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer.
Treatment with alpha-interferon to increase expression of target antigen on tumor surfaces has been moderately well-tolerated and resulted in a few clinical responses, according to the preliminary results of a phase II clinical trial described by James L. Murray, MD, of the University of Texas M.D. Anderson Cancer Center. Other speakers at the meeting described separate phase I dose-escalation trials of iodine(Drug information on iodine) 131-labeled and yttrium 90-labeled antibodies with autologous stem cell support.
The trial at M.D. Anderson was based on the observations that the TAG-72 antigen is expressed by breast cancer cells and that, in animal models, treatment with interferon led to improved targeting of TAG-72-directed radioimmunotherapy and an enhanced therapeutic response. A phase I study at Memorial Sloan-Kettering Cancer Center had previously shown that treatment with 131I-labeled CC49 (an anti-TAG-72 murine monoclonal antibody) resulted in favorable antibody targeting and limited toxicity in patients with breast cancer.
The primary aim of the present trial was to determine whether interferon could enhance targeting, biodistribution, and efficacy of radioimmunotherapy in patients with recurrent breast cancer. Fifteen patients were treated. All had skin or soft-tissue disease that was biopsied serially to measure tumor antigen up-regulation.
After the initial skin or lymph node biopsy was obtained, patients were randomized, with one group beginning daily alpha-interferon treatment. After 3 days, patients received a tracer dose of 131I-labeled CC49. Tumor biopsies were obtained 2 days later and analyzed immunohistochemically for antigen up-regulation.
Following dosimetry studies, all patients then received treatment with the antibody in amounts calculated to deliver less than 200 cGy to the bone marrow, resulting in doses of 60 to 75 mCi/m². The seven patients initially randomized to receive interferon continued to receive it for a total of 14 days. The second group began 14 days' treatment with interferon simultaneously with the radiolabeled antibody.
The serial immunohistochemistry studies showed a mean increase in tumor TAG-72 expression of 46% in patients pretreated with interferon-alpha, compared with minimal up-regulation in the control group. The calculated radiation dose to red marrow was increased by 15% to 20% in patients receiving interferon, compared with controls. Pretreatment also resulted in somewhat longer blood retention time of the radioantibody.