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Phase I safety, pha...
Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types
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Baselga, J (författare)
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Rischin, D (författare)
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Ranson, M (författare)
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visa fler...
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Calvert, H (författare)
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Raymond, E (författare)
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Kieback, D G (författare)
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Kaye, S B (författare)
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Gianni, L (författare)
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Harris, A (författare)
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- Björk, Thomas (författare)
- Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups
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Averbuch, S D (författare)
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Feyereislova, A (författare)
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Swaisland, H (författare)
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Rojo, F (författare)
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Albanell, J (författare)
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(creator_code:org_t)
- 2002
- 2002
- Engelska.
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 20:21, s. 4292-4302
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http://jco.ascopubs....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- Av författaren/redakt...
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Baselga, J
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Rischin, D
-
Ranson, M
-
Calvert, H
-
Raymond, E
-
Kieback, D G
-
visa fler...
-
Kaye, S B
-
Gianni, L
-
Harris, A
-
Björk, Thomas
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Averbuch, S D
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Feyereislova, A
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Swaisland, H
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Rojo, F
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Albanell, J
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visa färre...
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