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Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan

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Abstract

Background

Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated.

Methods

All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used.

Results

In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma.

Conclusion

Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

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Acknowledgments

We would like to express our deepest appreciation to the medical doctors participating in the Nexavar® SDUI in RCC and HCC in Japan as well as the reporting physicians for DLI patients for providing detailed information.

Conflict of interest

Y. H-Y. is an employee of Bayer Yakuhin, Ltd. A.G. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript. H.T. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript. Y.I. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript. F.S. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript. T.J. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript, those from Chugai Seiyaku, Ltd., as a member of the ILD Ad-board, and conducted honorary lectures with support from Daiichi-Sankyo Seiyaku, Ltd., Kyorin Seiyaku, Ltd., and Eizai Ltd. K.F. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript. S.K. has received consulting fees from Bayer Yakuhin, Ltd. as a member of the ILD Ad-board in the subject of this manuscript.

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Authors and Affiliations

  1. Pharmacovigilance, Medical Affairs, Bayer Yakuhin, Ltd., 4-9 Umeda 2-chome, Kita-ku, Osaka, 530-0001, Japan

    Yuka Horiuchi-Yamamoto

  2. Department of Pulmonary Medicine/Infection and Oncology, Internal Medicine, Nippon Medical School, Tokyo, 113-8603, Japan

    Akihiko Gemma

  3. Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, 489-8642, Japan

    Hiroyuki Taniguchi

  4. Department of Diffuse Lung Diseases and Respiratory Failure, Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, 591-8555, Japan

    Yoshikazu Inoue

  5. Department of Diagnostic Radiology, International Medical Center, Saitama Medical University, Hidaka, Saitama, 350-1298, Japan

    Fumikazu Sakai

  6. Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Hyogo, 664-8533, Japan

    Takeshi Johkoh

  7. Department of Radiology, Kurume University School of Medicine, and Center for Diagnostic Imaging, Kurume University Hospital, Kurume, Fukuoka, 830-0011, Japan

    Kiminori Fujimoto

  8. Fukujuji Hospital, Japan Anti-tuberculosis Association as Public Interest Incorporated Foundation, Kiyose, Tokyo, 204-8522, Japan

    Shoji Kudoh

Authors
  1. Yuka Horiuchi-Yamamoto
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  2. Akihiko Gemma
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  3. Hiroyuki Taniguchi
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  4. Yoshikazu Inoue
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  5. Fumikazu Sakai
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  6. Takeshi Johkoh
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  7. Kiminori Fujimoto
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  8. Shoji Kudoh
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Corresponding author

Correspondence to Yuka Horiuchi-Yamamoto.

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Cite this article

Horiuchi-Yamamoto, Y., Gemma, A., Taniguchi, H. et al. Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan. Int J Clin Oncol 18, 743–749 (2013). https://doi.org/10.1007/s10147-012-0438-0

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  • DOI: https://doi.org/10.1007/s10147-012-0438-0

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