Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid tumours

Kaye, S. et al. (2012) Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid tumours. British Journal of Cancer, 106(11), pp. 1728-1734. (doi:10.1038/bjc.2012.158)

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Abstract

Background: As a prelude to combination studies aimed at resistance reversal, this dose-escalation/dose-expansion study investigated the selective Src kinase inhibitor saracatinib (AZD0530) in combination with carboplatin and/or paclitaxel. Methods: Patients with advanced solid tumours received saracatinib once-daily oral tablets in combination with either carboplatin AUC 5 every 3 weeks (q3w), paclitaxel 175 mg m−2 q3w, paclitaxel 80 mg m−2 every 1 week (q1w), or carboplatin AUC 5 plus paclitaxel 175 mg m−2 q3w. The primary endpoint was safety/tolerability. Results: A total of 116 patients received saracatinib 125 (N=20), 175 (N=44), 225 (N=40), 250 (N=9), or 300 mg (N=3). There were no clear dose-related trends within each chemotherapy regimen group in number or severity of adverse events (AEs). However, combining all groups, the occurrence of grade 3 asthenic AEs (all causality) was dose-related (125 mg, 10%; 175 mg, 20%; 225 mg, 33%), and grade 3 neutropenia occurred more commonly at doses 225 mg. There was no evidence that saracatinib affected exposure to carboplatin or paclitaxel, or vice versa. Objective responses were seen in 5 out of 44 patients (11%) receiving carboplatin plus paclitaxel q3w, and 5 out of 24 (21%) receiving paclitaxel q1w. Conclusion:  Saracatinib doses up to 175 mg with paclitaxel with/without carboplatin showed acceptable toxicity in most patients, and are suitable for further trials.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jones, Professor Robert
Authors: Kaye, S., Aamdal, S., Jones, R., Freyer, G., Pujade-Lauraine, E., de Vries, E.G.E., Barriuso, J., Sandhu, S., Tan, D.S.-W., Hartog, V., Kuenen, B., Ruijter, R., Kristensen, G.B., Nyakas, M., Barrett, S., Burke, W., Pietersma, D., Stuart, M., Emeribe, U., and Boven, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
ISSN:0007-0920
Published Online:24 April 2012

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