Abstract
Preclinical studies have demonstrated that recombinant IFN-α (rIFN- α) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors. To determine whether rIFN-α could enhance TAG-72 expression in vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-α (3 x 106 units/m2 for 14 days) beginning on day 1 (group 1 = 7 patients) or on day 6 (group 2 = 8 patients). On day 3, all patients received a 10-20-mCi tracer dose of 131I-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m2 of 131I-CC49 on day 6. Whole body and single- photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases. Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients. Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment. For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 ± 4.7 versus 51.5 ± 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 ± 0.35 versus 1.07 ± 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-α was found to enhance TAG-72 expression in tumors from patients receiving rIFN-α (group 1) by 46 ± 19% (P < 0.05) compared to only 1.3 ± 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-α-treated patients. One partial and two minor tumor responses were seen. In summary, rIFN-α treatment altered the pharmacokinetics and tumor uptake of 131I-CC49 in patients at the expense of increased toxicity.
Original language | English (US) |
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Pages (from-to) | 1547-1555 |
Number of pages | 9 |
Journal | Clinical Cancer Research |
Volume | 3 |
Issue number | 9 |
State | Published - Sep 1997 |
ASJC Scopus subject areas
- Oncology
- Cancer Research