Annals of Oncology 14:922-930, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Japanese patients with solid malignant tumors
1 Kinki University School of Medicine, Osaka; 2 National Cancer Center Hospital, Tokyo; 3 Osaka City General Hospital, Osaka; 4 Osaka City University Medical School, Osaka, Japan; 5 AstraZeneca, Alderley Park, Macclesfield, UK; 6 AstraZeneca KK, Osaka, Japan
Received 31 July 2002; revised 29 November 2002; accepted 17 February 2003
Background:
This phase I dose-escalating study investigated the tolerability and toxicity of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Japanese patients with solid tumors. Thirty-one patients were included.
Patients and methods:
Patients initially received a single oral dose of gefitinib followed by 10–14 days of observation. Oral gefitinib was subsequently administered on 14 consecutive days, every 28 days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose-limiting toxicity (DLT).
Results:
Most adverse events were mild (grade 1/2); the most frequent were an acne-like rash and gastrointestinal effects. Two of six patients at 700 mg/day had DLT; no further dose escalation occurred. Cmax was reached within 3–7 h and exposure to gefitinib increased with dose. Mean terminal half-life following multiple dosing was 50.1 h (range 27.8–79.7 h). A partial response (duration 35–361 days) was observed in five of the 23 patients with non-small-cell lung cancer over a range of doses (225–700 mg/day), and seven patients with a range of tumors had disease stabilization (duration 40–127 days).
Conclusions:
In conclusion, gefitinib showed a favorable tolerability profile in Japanese patients. The safety profile, pharmacokinetic parameters and antitumor activity observed in our study are comparable to those observed in patients from the USA and Europe.
Key words: efficacy, EGFR inhibitor, gefitinib, ‘Iressa’, phase I trial, tolerability, ZD1839
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