A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours

Venugopal, B., Awada, A., Evans, T.R.J. , Dueland, S., Hendlisz, A., Rasch, W., Hernes, K., Hagen, S. and Aamdal, S. (2015) A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours. Cancer Chemotherapy and Pharmacology, 76(4), pp. 785-792. (doi: 10.1007/s00280-015-2846-0) (PMID:26289594)

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Abstract

Background: CP-4126 (gemcitabine elaidate, previously CO-101) is a lipid–drug conjugate of gemcitabine designed to circumvent human equilibrative nucleoside transporter1-related resistance to gemcitabine. The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of CP-4126, and to describe its pharmacokinetic profile. Methods: Eligible patients with advanced refractory solid tumours, and adequate performance status, haematological, renal and hepatic function, were treated with one of escalating doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and 15 of a 28-day cycle. Blood and urine samples were collected to determine the pharmacokinetics (PKs) of CP-4126. Results: Forty-three patients, median age 59 years (range 18–76; male = 27, female = 16), received one of ten dose levels (30–1600 mg/m2). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m2 on basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven patients achieved stable disease sustained for ≥3 months, including two patients with pancreatic cancer who had progressed on or after gemcitabine exposure. Conclusions: CP-4126 was well tolerated with comparable toxicity profile to gemcitabine. Future studies are required to determine its anti-tumour efficacy, either alone or in combination with other cytotoxic chemotherapy regimens.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Evans, Professor Jeff and Venugopal, Dr Balaji
Authors: Venugopal, B., Awada, A., Evans, T.R.J., Dueland, S., Hendlisz, A., Rasch, W., Hernes, K., Hagen, S., and Aamdal, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Chemotherapy and Pharmacology
Publisher:Springer Berlin Heidelberg
ISSN:0344-5704
ISSN (Online):1432-0843

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