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Advances Reported in Phase I/II Trials of Radioimmunotherapy for Breast Cancer

Advances Reported in Phase I/II Trials of Radioimmunotherapy for Breast Cancer

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 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.

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