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01-03-2008 | Original Article

Phase I dose-finding and pharmacokinetic study of the oral epidermal growth factor receptor tyrosine kinase inhibitor Ro50-8231 (erlotinib) in Japanese patients with solid tumors

Authors: Noboru Yamamoto, Atsushi Horiike, Yasuhito Fujisaka, Haruyasu Murakami, Tatsu Shimoyama, Yasuhide Yamada, Tomohide Tamura

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2008

Abstract

Purpose

The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors.

Patients and methods

Patients with solid tumors not amenable to standard forms of treatment were included. Treatment cycle 1 consisted of single-dose administration on day 1, withdrawal on day 2, continuous daily administration from days 3–23, and withdrawal from days 24–30. Subsequent cycles (28 days) used continuous daily administration. The dose of erlotinib was escalated from 50 mg/day to 150 mg/day in 50-mg increments. PK evaluation was performed in all patients during cycle 1.

Results

Fifteen patients, aged 38–70 (median; 57) years with non-small-cell lung (n = 11), colorectal (n = 3) or head and neck (n = 1) cancer were enrolled. The major toxicities were rash, diarrhea and liver dysfunctions, which were generally mild and easily manageable. The good tolerability of erlotinib up to the dose of 150 mg/day was confirmed. One patient developed grade 5 treatment-related interstitial pneumonitis. Four of 11 evaluable patients achieved partial responses; all four had non-small-cell lung cancer (NSCLC). The peak plasma concentration of erlotinib, and the area under the concentration-time curve increased proportionally to the dose, suggesting linear PK.

Conclusion

The recommended dose of erlotinib in Japanese patients is 150 mg/day. Further trials in Japanese NSCLC patients are warranted.

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Title: Phase I dose-finding and pharmacokinetic study of the oral epidermal growth factor receptor tyrosine kinase inhibitor Ro50-8231 (erlotinib) in Japanese patients with solid tumors
Authors: Noboru Yamamoto
Atsushi Horiike
Yasuhito Fujisaka
Haruyasu Murakami
Tatsu Shimoyama
Yasuhide Yamada
Tomohide Tamura
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-007-0494-8

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Abstract

Purpose

Patients and methods

Results

Conclusion

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