This post is in the 'cancer consultation' category..Tarceva trials..ARGH!..They already know that Tarceva has minimal monotherapy activity in the pre-treated population.here they're doing one PK study and one marker..If I wanted my loved one to live longer, I'd stay clear of these..they had underwhelming results in 2004..fwiw,
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Safety and Pharmacokinetics Study of Erlotinib (Tarceva) to Treat Patients With Recurrent Glioblastoma Multiforme.
UNC Lineberger Comprehensive Cancer Center
Genentech
We are proposing a novel dose escalation scheme of erlotinib, administered at 3-day intervals to patients with glioblastoma multiforme (GBM), a type of brain tumor. Our hypothesis is that a higher dose administered at 3-day intervals will achieve a more effective and less toxic alternative to daily dosing. In addition, we will examine the metabolism of erlotinib by specific liver enzymes and determine how well erlotinib penetrates the blood-brain-barrier in order to reach target site(s).
clinicaltrials.gov
A phase II trial of erlotinib (OSI-774) in patients (pts) with recurrent malignant gliomas (MG) not on EIAEDs.
Sub-category: CNS Tumors
Category: Central Nervous System Tumors
Meeting: 2004 ASCO Annual Meeting
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Abstract No: 1502
Citation: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 1502
Author(s): J. J. Raizer, L. E. Abrey, P. Wen, T. Cloughesy, I. A. Robins, H. A. Fine, F. Lieberman, V. K. Puduvalli, K. L. Fink, M. Prados; Northwestern University, Feinberg School of Medicine, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; University of California, Los Angeles, Los Angeles, CA; University of Wisconsin Hospital & Clinics, Madison, WI; Neuro-Oncology Branch, NCI, NIH, Bethesda, MD; University of Pittsburgh, Pittsburgh, PA; U Texas M. D. Anderson Cancer Center, Houston, TX; U Texas Southwestern Medical Center, Dallas, TX; University of California, San Francisco, CA
Abstract: Purpose: To evaluate the efficacy of OSI-774, a small molecule tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), in patients with recurrent malignant gliomas not on enzyme induce anti-convulsant drugs (EIAEDs). Methods: Pts with recurrent MG were treated with OSI-774 at a dose of 150 mg/day continuously. Patients could not have had more than 2 prior chemotherapies. Patients were evaluated for response with MRI every 56 days. PK studies and AGP levels were done in most patients. Results: 67 pts enrolled onto this arm of the study but only the 45 pts with recurrent MG are reported here. Histology: 30 (20M/10F) pts had glioblastoma multiformes (GBMs) and 15 (7M/8F) pts had anaplastic gliomas (AGs). Median age and KPS was 58 years and 80 for GBMs and 43 years and 90 for AGs. The median PFS for GBM was 12 wks (95% CI; 7.6 to 13 weeks) with no GBM pts progression free at 24 weeks; best response was SD in 4 pts. For AGs median PFS was 8.6 wks (CI; 3.7 to 45 wks) with 4 patients still on study; best response was 1 PR (unconfirmed) and 2 SD. Cycle 1 toxicities: Gr 3-Rash and hypokalemia all others were Gr 1 and 2, primarily rash, diarrhea, fatigue, and bilirubin elevation. PK studies on 20 pts, found an AUC0-24 for OSI-774 was 13.1 ugxh/ml and for OSI-420 875 ngxh/ml; the Cpmax (ng/ml) was 895 and 64 for OSI-774 and OSI-420. Conclusion: We completed a phase II trial of OSI-774 in patients with MGs not on EIAEDs. While a few patients had SD and 1 had a PR the median PFS and the 24 week PFS suggest that for GBMs and AGs that OSI-774 has limited activity as a single agent. Toxicities were primarily Gr 1 and 2 and tolerable.
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