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Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics

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Abstract

Background

We conducted a phase II trial of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and evaluated the relationship between plasma concentration and efficacy of erlotinib.

Methods

Patients who were previously treated but naive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), with advanced NSCLC harboring EGFR mutations, were enrolled. Erlotinib was given at 150 mg once daily until disease progression. The primary end point was objective response rate (ORR). Plasma trough levels of erlotinib were measured on Days 2 (D2) and 8 (D8) by high-performance liquid chromatography.

Results

In total, 29 patients were enrolled from September 2008 to January 2011. ORR was 61.5 % (95 % confidence interval [CI] 40.57–79.8) of 26 assessable patients. The median progression-free survival (PFS) and overall survival (OS) were 6.3 months and 16.9 months, respectively. Skin rash was observed in 24 patients, mostly at grade 1 or 2. Grade 2 pneumonitis was observed in one patient. We collected blood samples from 16 patients. The median PFS of the high and low D8/D2 ratio group was 11.2 months and 5.7 months, respectively (p = 0.044, hazard ratio = 0.301, 95 % CI 0.094–0.968).

Conclusion

Erlotinib showed an ORR comparable to that seen in previous studies for patients with NSCLC harboring EGFR mutations, although response, the primary end point, did not reach the predetermined threshold level. The D8/D2 ratio of erlotinib plasma trough levels might be a predictive factor for PFS.

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Conflict of interest

We confirm that this report has not been published or presented elsewhere, either in whole or in part, and that it is not under consideration by another journal. All authors have approved the content and agree with its submission. No financial support was received for this publication, and neither my co-authors nor I have any conflict of interest to declare.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Kohei Motoshima, Yoichi Nakamura, Takaya Ikeda, Kosuke Mizoguchi, Shinnosuke Takemoto, Seiji Nagashima, Tetsuya Iida & Shigeru Kohno

  2. Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University, Tokyo, Japan

    Kazumi Sano & Yoji Ikegami

  3. Department of Respiratory Medicine, Japanese Red-Cross Nagasaki Atomic Bomb Hospital, Nagasaki, Japan

    Minoru Fukuda

  4. Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Kazuhiro Tsukamoto

Authors
  1. Kohei Motoshima
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  2. Yoichi Nakamura
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  3. Kazumi Sano
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  4. Yoji Ikegami
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  5. Takaya Ikeda
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  8. Minoru Fukuda
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  9. Seiji Nagashima
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  11. Kazuhiro Tsukamoto
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  12. Shigeru Kohno
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Corresponding author

Correspondence to Yoichi Nakamura.

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Motoshima, K., Nakamura, Y., Sano, K. et al. Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics. Cancer Chemother Pharmacol 72, 1299–1304 (2013). https://doi.org/10.1007/s00280-013-2307-6

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  • DOI: https://doi.org/10.1007/s00280-013-2307-6

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