TY - JOUR
T1 - The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours
T2 - Results of a phase Ib dose-escalation, open-label study
AU - Molife, L. R.
AU - Fong, P. C.
AU - Paccagnella, L.
AU - Reid, A. H.M.
AU - Shaw, H. M.
AU - Vidal, L.
AU - Arkenau, H. T.
AU - Karavasilis, V.
AU - Yap, T. A.
AU - Olmos, D.
AU - Spicer, J.
AU - Postel-Vinay, S.
AU - Yin, D.
AU - Lipton, A.
AU - Demers, L.
AU - Leitzel, K.
AU - Gualberto, A.
AU - De Bono, J. S.
N1 - Funding Information:
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 Siân Marshall at ACUMED (Tytherington, UK) and was funded by Pfizer Inc.
Funding Information:
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).
PY - 2010/7/27
Y1 - 2010/7/27
N2 - 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 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m-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 3≥mg 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.
AB - 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 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m-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 3≥mg 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.
KW - chemosensitisation
KW - docetaxel
KW - figitumumab (CP-751,871)
KW - insulin-like growth factor type 1 receptor (IGF-IR)
KW - monoclonal antibody
UR - http://www.scopus.com/inward/record.url?scp=77955049754&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6605767
DO - 10.1038/sj.bjc.6605767
M3 - Article
C2 - 20628389
AN - SCOPUS:77955049754
SN - 0007-0920
VL - 103
SP - 332
EP - 339
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -