ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial.

2.50
Hdl Handle:
http://hdl.handle.net/2436/29454
Title:
ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial.
Authors:
Ranson, Malcolm; Hammond, Lisa A.; Ferry, David R.; Kris, Mark; Tullo, Andrew; Murray, Philip I.; Miller, Vince; Averbuch, Steve; Ochs, Judy; Morris, Charles; Feyereislova, Andrea; Swaisland, Helen; Rowinsky, Eric K.
Abstract:
PURPOSE: To investigate the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS: This was an open, phase I, escalating multiple-dose tolerability and pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days followed by 14 days off treatment. Dose escalation started at 50 mg/d and continued to 925 mg or until consistent dose-limiting toxicity (DLT) was observed. RESULTS: Sixty-four patients were entered at eight dose levels. The most frequent dose-related grade 1 and 2 adverse events were an acne-like (or folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700 mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half-life was 48 hours (range, 37 to 65). Four of 16 patients with non-small-cell lung cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700 mg/d. Overall, 16 patients remained on study for > or = 3 months, with seven of these patients (five with NSCLC, including three of the patients with partial response) remaining on study for > or = 6 months. CONCLUSION: ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.
Citation:
Journal of Clinical Oncology, 20(9): 2240-2250
Publisher:
American Society of Clinical Oncology
Journal:
Journal of Clinical Oncology
Issue Date:
2002
URI:
http://hdl.handle.net/2436/29454
PubMed ID:
11980995
Additional Links:
http://jco.ascopubs.org/cgi/content/full/20/9/2240
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
Cancer Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorRanson, Malcolm-
dc.contributor.authorHammond, Lisa A.-
dc.contributor.authorFerry, David R.-
dc.contributor.authorKris, Mark-
dc.contributor.authorTullo, Andrew-
dc.contributor.authorMurray, Philip I.-
dc.contributor.authorMiller, Vince-
dc.contributor.authorAverbuch, Steve-
dc.contributor.authorOchs, Judy-
dc.contributor.authorMorris, Charles-
dc.contributor.authorFeyereislova, Andrea-
dc.contributor.authorSwaisland, Helen-
dc.contributor.authorRowinsky, Eric K.-
dc.date.accessioned2008-06-04T09:22:05Z-
dc.date.available2008-06-04T09:22:05Z-
dc.date.issued2002-
dc.identifier.citationJournal of Clinical Oncology, 20(9): 2240-2250en
dc.identifier.issn0732-183X-
dc.identifier.pmid11980995-
dc.identifier.urihttp://hdl.handle.net/2436/29454-
dc.description.abstractPURPOSE: To investigate the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS: This was an open, phase I, escalating multiple-dose tolerability and pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days followed by 14 days off treatment. Dose escalation started at 50 mg/d and continued to 925 mg or until consistent dose-limiting toxicity (DLT) was observed. RESULTS: Sixty-four patients were entered at eight dose levels. The most frequent dose-related grade 1 and 2 adverse events were an acne-like (or folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700 mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half-life was 48 hours (range, 37 to 65). Four of 16 patients with non-small-cell lung cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700 mg/d. Overall, 16 patients remained on study for > or = 3 months, with seven of these patients (five with NSCLC, including three of the patients with partial response) remaining on study for > or = 6 months. CONCLUSION: ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.en
dc.language.isoenen
dc.publisherAmerican Society of Clinical Oncologyen
dc.relation.urlhttp://jco.ascopubs.org/cgi/content/full/20/9/2240en
dc.subject.meshAdministration, Oralen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshArea Under Curveen
dc.subject.meshDose-Response Relationship, Drugen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshNeoplasmsen
dc.subject.meshProtein-Tyrosine Kinasesen
dc.subject.meshQuinazolinesen
dc.subject.meshReceptor, Epidermal Growth Factoren
dc.subject.meshTreatment Outcomeen
dc.titleZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial.en
dc.typeArticleen
dc.identifier.journalJournal of Clinical Oncologyen

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