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The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study

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Molife, L. R., Fong, P. C., Paccagnella, L., Reid, A. H. M., Shaw, H. M., Vidal, L., Arkenau, H., Karavasilis, V., Yap, T. A., Olmos, D., Spicer, J., Postel-Vinay, S., Yin, D., Lipton, A., Demers, L., Leitzel, K., Gualberto, A., de Bono, J. S. (2010) The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study. BRITISH JOURNAL OF CANCER, 103 (3). pp. 332-339. ISSN 0007-0920

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A copy of the full text may be available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC29200...

Abstract

BACKGROUND: This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type I receptor (IGF-IR), in combination with docetaxel. METHODS: Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mgm (2) docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated. RESULTS: In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n = 28), febrile neutropaenia (n = 11), fatigue (n = 10), leukopaenia (n = 7), diarrhoea (n = 5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n = 1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of >= 6 months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of >= 3mg kg(-1). Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had >= 5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from >= 5 to <5 CTCs and 9 out of 10 (90%) had a >= 30% decline in CTCs after therapy. CONCLUSIONS: Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted. British Journal of Cancer (2010) 103, 332-339. doi:10.1038/sj.bjc.6605767 www.bjcancer.com Published online 13 July 2010 (C) 2010 Cancer Research UK

Item Type: Article
Authors (ICR Faculty only): De-Bono, Johann
All Authors: Molife, L. R., Fong, P. C., Paccagnella, L., Reid, A. H. M., Shaw, H. M., Vidal, L., Arkenau, H., Karavasilis, V., Yap, T. A., Olmos, D., Spicer, J., Postel-Vinay, S., Yin, D., Lipton, A., Demers, L., Leitzel, K., Gualberto, A., de Bono, J. S.
Uncontrolled Keywords: figitumumab (CP-751,871); insulin-like growth factor type I receptor (IGF-IR); chemosensitisation; monoclonal antibody; docetaxel;MONOCLONAL-ANTIBODY CP-751,871; RESISTANT PROSTATE-CANCER; BREAST-CANCER; IGF-II; CELLS; EXPRESSION; SYSTEM
Funding Acknowledgement: Pfizer Inc. ; Cancer Research UK ; Experimental Cancer Medicine Centre ; National Institute for Health Research Biomedical Research Centre
Funding Text: This study was sponsored by Pfizer Inc. The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support was also provided by the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) and the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research). We thank all of the participating patients and their families, as well as the global network of investigators, research nurses, study coordinators, and operations staff. Editorial/medical writing support was provided by Sian Marshall at ACUMED (Tytherington, UK) and was funded by Pfizer Inc.
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: 31 Aug 2010 15:25
Last Modified: 11 Jul 2017 09:18
URI: http://publications.icr.ac.uk/id/eprint/9849

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