Abstract
Background
Masitinib is a tyrosine kinase inhibitor with a pre-clinical profile suggesting greater
affinity and selectivity in vitro for the wild-type c-Kit receptor and its juxtamembrane mutation than imatinib.
Methods
This dose-escalation study was conducted in patients with advanced and/or metastatic
cancer to determine the maximum tolerated dose (MTD) for orally administered masitinib
over a 12-week period. Secondary objectives were a clinical assessment of masitinib’s
activity in cancer patients and establishment of a pharmacokinetic profile.
Results
Forty patients with various solid tumours (predominantly GIST, 19 patients) were treated
with masitinib at doses ranging between 0.7 and 17.2 mg/kg/day. Although the MTD was not formally reached, an acceptable dose for chronic
use was identified at 12 mg/kg/day. Treatment-related AEs were frequent (38/40 patients), however, the majority
were grade 1 or 2 and demonstrated dose dependency at higher concentrations. Pharmacokinetic
results showed a linear, dose-dependent increase of Cmax and AUC. One of two GIST patients with imatinib intolerance had a partial response
at 11.1 mg/kg/day. About 29% of the imatinib-resistant GIST population and 38% of the overall
population had stable disease.
Conclusions
The safety profile of masitinib at 12 mg/kg/day b.i.d. for the treatment of solid cancers appears favourable and compatible with a long-term
regimen. Tumour control rate in imatinib-resistant patients was encouraging, hence,
the activity of masitinib in c-Kit expressing tumours, such as GIST, warrants further
exploration as first-line anticancer therapy as well as for imatinib-resistant patients.
Keywords
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Article info
Publication history
Published online: June 22, 2009
Accepted:
May 7,
2009
Received:
April 29,
2009
Identification
Copyright
© 2009 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
