Macpherson, I.R. , Poondru, S., Simon, G.R., Gedrich, R., Brock, K., Hopkins, C.A., Stewart, K., Stephens, A. and Evans, T.R.J. (2013) A phase 1 study of OSI-930 in combination with erlotinib in patients with advanced solid tumours. European Journal of Cancer, 49(4), pp. 782-789. (doi: 10.1016/j.ejca.2012.09.036)
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Abstract
Aim: To determine the maximum tolerated dose (MTD) of OSI-930 that can be combined with erlotinib, and establish recommended phase 2 doses when both agents are administered daily in patients with advanced solid tumours. Patients and methods: Eligible patients with advanced solid tumours were enrolled into this standard “three + three” dose escalation study. Study treatment commenced on day 1 with OSI-930, and erlotinib was introduced on day 8. PK profiles of OSI-930, erlotinib and its active metabolite, OSI-420, were determined. Changes in sVEGFR2 as a pharmacodynamic biomarker of OSI-930 activity were assessed. Results: Twenty one patients were enrolled to 1 of 3 cohorts: 200 mg OSI-930 BID + 100 mg erlotinib QD; 200 mg OSI-930 BID + 150 mg erlotinib QD; 300 mg OSI-930 BID + 150 mg erlotinib QD. The most common adverse events were anorexia (85%), diarrhoea (75%), rash (70%) and lethargy (65%). The MTD was not reached but the onset of cumulative toxicity necessitating dose modification after the 28-d DLT assessment period was common at the highest dose level. A PK interaction was identified with co-administration of both agents resulting in a two-fold increase in OSI-930 exposure. Pharmacodynamic activity was observed with a decline in sVEGFR levels detected in all patients. Ten patients had disease stabilization (median duration 119 d). Conclusions: 200 mg OSI-930 BID + 150 mg erlotinib QD were the recommended doses for further evaluation of this combination.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | MacPherson, Professor Iain and Evans, Professor Jeff |
| Authors: | Macpherson, I.R., Poondru, S., Simon, G.R., Gedrich, R., Brock, K., Hopkins, C.A., Stewart, K., Stephens, A., and Evans, T.R.J. |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | European Journal of Cancer |
| Publisher: | Elsevier |
| ISSN: | 0959-8049 |
| Published Online: | 22 October 2012 |
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