title: One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sorafenib therapy for advanced renal cell carcinoma in Japanese patients.
abstract: BACKGROUND
  Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study.
  
  
  METHODS
  A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1 month (1M-RDI).
  
  
  RESULTS
  There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ≥ 50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1 months (95% I collagen (95% CI): 2.0-6.2), whereas it was 10.5 months (95% CI: 7.6-13.4) in the patients with 1M-RDI of ⩾50% (P=0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658-8.883, P=0.002) but not OS (P=0.328).
  
  
  CONCLUSIONS
  Although this study was retrospective, a 1M-RDI cut-off value of ≥ 50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsunari
authors.initials: A
authors.lastname: Kawashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takayama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.forename: Go
authors.initials: G
authors.lastname: Tanigawa
authors.forename: Mikio
authors.initials: M
authors.lastname: Nin
authors.forename: Jiro
authors.initials: J
authors.lastname: Kajikawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Imazu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasunaga
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Kenji
authors.initials: K
authors.lastname: Nishimura
authors.forename: Shingo
authors.initials: S
authors.lastname: Takada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishimura
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage*; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib