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

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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
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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