Abstract | PURPOSE: PATIENTS AND METHODS: RESULTS: No significant side effects were observed up to a total dose of 600 mg/m2. Based on tyrosine kinase activity, a high degree of EGFR saturation (> or = 50%) was observed at doses > or = 200 mg/m2, and EGFR saturation was estimated to be 100% at a dose level of 600 mg/m2 both in tumor tissue and skin used as surrogate EGFR-positive tissue. Immunohistochemistry studies showed that RG 83852 localized in tumor tissue and skin, but not in stroma, at doses > or = 400 mg/m2, and high EGFR saturation was observed at 600 mg/m2. Tumor EGFR tyrosine kinase activity was studied in five patients (four with EGFR-positive tumors) before and 24 hours post- therapy; a threefold to fourfold upregulation of EGFR tyrosine kinase activity in posttherapy specimens was observed in two patients. Moderate upregulation of EGFR itself was suggested in both of these patients and in two additional patients by immunohistochemistry. CONCLUSION:
RG 83852 causes no toxic effects at doses that result in high tumor EGFR saturation. Treatment with RG 83852 may enhance EGFR tyrosine kinase activity and/or EGFR expression. Because high EGFR expression by tumors has been associated with increased sensitivity to cytotoxic therapy, the suggestion of antibody-mediated upregulation of EGFR by agents such as RG 83852 may prove useful in enhancing chemotherapeutic efficacy.
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Authors | R Perez-Soler, N J Donato, D M Shin, M G Rosenblum, H Z Zhang, C Tornos, H Brewer, J C Chan, J S Lee, W K Hong |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 12
Issue 4
Pg. 730-9
(Apr 1994)
ISSN: 0732-183X [Print] United States |
PMID | 8151316
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- RG 83852 monoclonal antibody
- ErbB Receptors
- Protein-Tyrosine Kinases
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Topics |
- Antibodies, Monoclonal
(administration & dosage, pharmacology, therapeutic use)
- Antibodies, Monoclonal, Murine-Derived
- Carcinoma, Non-Small-Cell Lung
(metabolism, therapy)
- ErbB Receptors
(metabolism)
- Head and Neck Neoplasms
(metabolism, therapy)
- Humans
- Immunohistochemistry
- Infusions, Intravenous
- Lung Neoplasms
(metabolism, therapy)
- Protein-Tyrosine Kinases
(metabolism)
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