Phase I dose escalation study of the anti-insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors
Haluska, P., Shaw, H. M., Batzel, G. N., Yin, D., Molina, J. R., Molife, L. R., Yap, T. A., Roberts, M. L., Sharma, A., Gualberto, A., Adjei, A. A., de Bono, J. S.
(2007)
Phase I dose escalation study of the anti-insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors.
CLINICAL CANCER RESEARCH, 13 (19).
pp. 5834-5840.
ISSN 1078-0432
Full text not available from this repository.
Abstract
Purpose: This phase I study was undertaken to define the maximum tolerated dose, safety, and pharmacokinetic profile of CP-751,871. Experimental Design: Using a rapid dose escalation design, patients with advanced nonhematologic malignancies were treated with CP-751,871 in four dose escalation cohorts. CP-751,871 was administered i.v on day 1 of each 21 -day cycle. Pharmacokinetic evaluation was done in all *treatment cohorts during cycles 1 and 4. Results: Twenty-four patients received 110 cycles at four dose levels. The maximum tolerated dose exceeded the maximal feasible dose of 20 mg/kg and, thus, was not identified. Treatment-related toxicities were generally mild. The most common adverse events were hyperglycemia, anorexia, nausea, elevated aspartate aminotransferase, elevated -gamma-glutamyltransferase, diarrhea, hyperuracemia, and fatigue. At 20 mg/kg, 10 of 15 patients experienced stability of disease. Two of these patients experienced long-term stability, There were no objective responses. Pharmacokinetic analysis revealed a dose-dependent increase in CP-751,871 exposure and - 2-fold accumulation on repeated dosing in 21 -day cycles. Plasma concentrations of CP-751,871 attained were several log-fold greater than the biologically active concentration. Treatment with CP-751,871 increased serum insulin and human growth hormone levels, with modest increases in serum glucose levels. Conclusions: CP-751,871 has a favorable safety profile and was well tolerated when given in continuous cycles. At the maximal feasible dose of 20 mg/kg, there was a moderate accumulation in plasma exposure, and most of the treated patients experienced stability of disease.
Item Type: | Article |
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Authors (ICR Faculty only): | De-Bono, Johann |
All Authors: | Haluska, P., Shaw, H. M., Batzel, G. N., Yin, D., Molina, J. R., Molife, L. R., Yap, T. A., Roberts, M. L., Sharma, A., Gualberto, A., Adjei, A. A., de Bono, J. S. |
Uncontrolled Keywords: | FACTOR-BINDING PROTEIN-3; BREAST-CANCER CELLS; IGF-I; COLORECTAL-CANCER; INDUCED APOPTOSIS; MULTIPLE-MYELOMA; WILD-TYPE; EXPRESSION; RISK; INHIBITION |
Research teams: | ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group |
Depositing User: | Users 10 not found. |
Date Deposited: | 26 Nov 2007 12:22 |
Last Modified: | 11 Jul 2017 09:57 |
URI: | http://publications.icr.ac.uk/id/eprint/5392 |
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