title: Phase I/II study of amrubicin in combination with S-1 as second-line chemotherapy for non-small-cell lung cancer without EGFR mutation.
abstract: BACKGROUND
  Both amrubicin (Am) and S-1 are effective against non-small-cell lung cancer (NSCLC), and preclinical studies have demonstrated that the effect of tegafur/uracil, the original compound of S-1, in combination with Am significantly inhibits tumor growth.
  
  
  METHODS
  We conducted a phase I/II study of Am and S-1 against pretreated NSCLC without EGFR mutation. We fixed the dose of S-1 at 40 mg/m(2) on days 1-14 and escalated the Am dose in increments of 5 mg/m(2) from a starting dose of 30 mg/m(2)/day on days 1-3 and repeated the cycle every 4 weeks.
  
  
  RESULTS
  Twenty-six patients were registered. In phase I, at an Am dose of 35 mg/m(2)/day, three patients experienced grade 2 leukopenia during S-1 administration, and S-1 was withdrawn. Another patient developed grade 2 serum bilirubin in the first cycle. DLTs were observed in four of six patients at this dose level, and therefore, 30 mg/m(2)/day was set as the recommended dose for Am. Twenty patients received this recommended Am dose. Febrile neutropenia was observed in two patients, and one patient developed a grade 4 increase in serum creatinine. Grade 3 vomiting, infection, hypotension, and urinary retention were observed in one patient each, respectively. Other toxicities were mild, and there were no treatment-related deaths. Two patients showed a CR, three showed a PR, and the overall response rate was 25.0%. The median progression-free and the median survival times were 3.8 and 15.6 months, respectively, and the 1-year survival rate was 60%.
  
  
  CONCLUSIONS
  Am and S-1 every 4 weeks is an effective combination for pretreated NSCLC without EGFR mutation.
authors: Department of Thoracic Oncology, Kanagawa Cancer Center, Nakao 1-1-2, Asahi-ku, Yokohama 241-0815, Japan.
authors: Shuji
authors: S
authors: Murakami
authors: Fumihiro
authors: F
authors: Oshita
authors: Makiko
authors: M
authors: Sugiura
authors: Tetsuro
authors: T
authors: Kondo
authors: Haruhiro
authors: H
authors: Saito
authors: Kouzo
authors: K
authors: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010094:Oxonic Acid / Q000008:administration & dosage; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C055866:amrubicin; D066246:ErbB Receptors