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Cancer Chemotherapy and Pharmacology

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01.01.2012 | Clinical Trial Report

Safety and pharmacokinetics of high-dose gefitinib in patients with solid tumors: results of a phase I study

verfasst von: Mitchell E. Gross, Lawrence Leichman, Elizabeth S. Lowe, Alan Swaisland, David B. Agus

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2012

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Abstract

Purpose

Previous studies established the safety of continuous gefitinib 250 or 500 mg daily. It was postulated that a higher dose may have increased efficacy by inhibiting signaling in both the mitogen-activated protein kinase and AKT pathways. This study investigated the tolerability, pharmacokinetics, and antitumor activity of high-dose gefitinib in patients with refractory solid malignancies.

Methods

Sequential cohorts received oral gefitinib once or twice-weekly, with dose escalation from 1,500 to 3,500 mg.

Results

Twenty-three patients received gefitinib at seven dose levels (1,500, 2,000, 2,500, 3,000, and 3,500 mg once-weekly; 1,500 and 2,000 mg twice-weekly). Gefitinib was well tolerated, with no dose-limiting toxicities. The maximum tolerated dose was not reached. The most common gefitinib-related adverse events were nausea and diarrhea, vomiting, and rash. Pharmacokinetic data demonstrated no consistent increase in exposure to gefitinib with increasing dose across cohorts. Consequently, the study was stopped early and gefitinib 2,000 mg twice-weekly was the highest dose administered. One of eight patients with non-small-cell lung cancer achieved a partial response.

Conclusions

Exposure to gefitinib did not increase consistently with increasing dose beyond gefitinib 1,500 mg once-weekly or twice-weekly. These data do not support further evaluation of gefitinib at high-dose schedules.

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Titel: Safety and pharmacokinetics of high-dose gefitinib in patients with solid tumors: results of a phase I study
verfasst von: Mitchell E. Gross
Lawrence Leichman
Elizabeth S. Lowe
Alan Swaisland
David B. Agus
Publikationsdatum: 01.01.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1757-y

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24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Safety and pharmacokinetics of high-dose gefitinib in patients with solid tumors: results of a phase I study

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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