title: EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with non-small cell lung cancer with acquired resistance to gefitinib.
abstract: EKB-569 is a potent, low molecular weight, selective, and irreversible inhibitor of epidermal growth factor receptor (EGFR) that is being developed as an anticancer agent. A phase 1, dose-escalation study was conducted in Japanese patients. EKB-569 was administered orally, once daily, in 28-day cycles, to patients with advanced-stage malignancies known to overexpress EGFR. Two patients with advanced non-small cell lung cancer with EGFR mutations and acquired gefitinib resistance from the phase 1 study are described in detail. Case #1 is a 63-year-old man with smoking history. He received treatment from 4 March 2004. Because he had no severe adverse events, a total of 10 courses of therapy were completed through December 16. Grade 2 skin rash and ALT elevation, and grade 1 diarrhea and nail changes developed. A chest CT scan on 4 August 2003 revealed multiple pulmonary metastases that had decreased in size. Case #2 is a 49-year-old woman with no smoking history. She received therapy from 9 February 2004. She received a total of five courses of the therapy until 22 June 2004. Grade 3 nausea and vomiting and grade 1 diarrhea and dry skin developed. A chest CT scan on March 3 revealed multiple pulmonary metastases that had decreased in size. A brain MRI on March 4 showed that multiple brain metastases also had decreased in size. Based on RECIST criteria, they had stable disease but radiographic tumor regression was observed.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Osaka 545-8585, Japan. y-naruo@sc4.so-net.ne.jp
authors.forename: Naruo
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kimura
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mitsuoka
authors.forename: Kuniomi
authors.initials: K
authors.lastname: Matsuura
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsui
authors.forename: Shunichi
authors.initials: S
authors.lastname: Negoro
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000284:Administration, Oral; D000634:Aminoquinolines; D000814:Aniline Compounds; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000634:Aminoquinolines; D000814:Aniline Compounds; D009930:Organic Chemicals; D011799:Quinazolines; D000077156:Gefitinib; C413879:EKB 569