Affiliations: Translational Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan | Translational Research Informatics Center, Kobe, Japan
Note: [] The first and second authors contributed equally.
Note: [] Corresponding author: Tsutomu Nishimura, Translational Research Center, Graduate School of Medicine, Kyoto University, Shogoin Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: +81 75 751 3397; Fax: +81 75 751 3399; E-mail: [email protected].
Abstract: Objective: In a previous paper, we described the major health tragedy that occurred in Japan involving the use of gefitinib, and recommended steps to prevent such problems occurring again. In that paper, we argued that erlotinib should only be approved on the condition that all users are subject to surveillance. Erlotinib was subsequently approved for use in Japan on October 19, 2007. In the present paper, we examine whether our recommendations have been implemented in the safety measures established for erlotinib use. Methods: We comprehensively reviewed reports regarding erlotinib treatment published between 2007 and 2009 by regulatory agencies and the manufacturer of the erlotinib-containing drug. We evaluated the safety measures established for erlotinib in view of three problems we identified with the treatment of gefitinib marketing: (1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly incorporated into the product information; (2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and (3) despite many serious cases of interstitial lung disease being spontaneously reported, well-designed post-marketing surveillance was not conducted immediately after these problems became evident. Results: We found that appropriate measures were taken for erlotinib in relation to each of the three above-mentioned problems. We found that there were fewer fatal adverse reactions to erlotinib after marketing relative to the pre-marketing period. Conclusions: Our recommendations following the health tragedy caused by gefitinib were implemented in the safety measures for erlotinib, which probably explains the smaller number of fatal adverse reactions to erlotinib in post-marketing surveillance than in pre-marketing trials.
