title: A phase I dose-escalation study of eribulin and S-1 for metastatic breast cancer.
abstract: BACKGROUND
  We evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, recommended dose for phase II (P2RD), and preliminary anticancer activity of a combination eribulin and S-1 therapeutic in metastatic breast cancer patients pretreated with anthracycline and taxane.
  
  
  METHODS
  Patients aged 20-74 years were recruited. In level 1, patients received S-1 (65 mg m(-2)) from day 1 to 14, and eribulin (1.1 mg m(-2)) on day 1 and 8 in a 21-day cycle. In level 2, eribulin was increased to 1.4 mg m(-2). In level 3, S-1 was increased to 80 mg m(-2).
  
  
  RESULTS
  Twelve patients were enrolled into three cohorts. Planned dose escalation was completed, with one case exhibiting dose-limiting toxicity (grade 3 hypokalaemia) at level 3, without reaching the MTD. The P2RD was determined to be level 2 (eribulin 1.4 mg m(-2) and S-1 65 mg m(-2)). The most common grade 3 or 4 toxicity was neutropenia (83.3%), followed by febrile neutropenia (25.0%). Five of eleven patients (41.7%) with measurable disease had a partial response. Pharmacokinetics were characterised by dose-dependent elimination and nonlinear exposure.
  
  
  CONCLUSIONS
  Dose level 3 was not tolerated owing to febrile neutropenia development. Thus, intermediate dose level 2 was recommended for further evaluation. Preliminary antitumour activity warrants further investigation in this setting.
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: T
authors: T
authors: Sakiyama
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: J
authors: J
authors: Tsurutani
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: T
authors: T
authors: Iwasa
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: H
authors: H
authors: Kawakami
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: Y
authors: Y
authors: Nonagase
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: T
authors: T
authors: Yoshida
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: K
authors: K
authors: Tanaka
authors: Clinical Research Center, Osaka Medical Collage Hospital, 2-7 Daigaku-cho, Takatsuki 569-8686, Japan.
authors: Y
authors: Y
authors: Fujisaka
authors: Department of Thoracic Oncology, Kansai Medical University Hirakata Hospital, 2-3-1 Shinmachi, Hirakata 573-1191, Japan.
authors: T
authors: T
authors: Kurata
authors: Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: Y
authors: Y
authors: Komoike
authors: Department of Genome Biology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: K
authors: K
authors: Nishio
authors: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-sayama 589-8511, Japan.
authors: K
authors: K
authors: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005663:Furans / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007659:Ketones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult; D000095662:Polyether Polyketides
chemical_list: D004338:Drug Combinations; D005663:Furans; D007659:Ketones; D010094:Oxonic Acid; D005641:Tegafur; C079198:S 1 (combination); C490954:eribulin; D000095662:Polyether Polyketides
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