title: Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan.
abstract: BACKGROUND
  To improve antitumor effects against metastatic renal cell carcinoma (mRCC), use of molecular target-based drugs in sequential or combination therapy has been advocated. In combination therapy, interferon (IFN)-α amplified the effect of sorafenib in our murine model (J Urol 184:2549, 2010), and cytokine-treated mRCC patients in Japan had good prognoses (Eur Urol 57:317, 2010). We thus conducted a phase II clinical trial of sorafenib plus IFN-α for untreated mRCC patients in Japan.
  
  
  METHODS
  In this multicenter, prospective study, provisionally registered patients with histologically confirmed metastatic clear cell RCC received natural IFN-α (3 dosages of 3 million U per week) for 2 weeks. Only IFN-α-tolerant patients were registered to this trial, and treated additionally with oral sorafenib (400 mg, bid). The primary end point of the study was rate of response (CR + PR) to sorafenib plus IFN-α treatment assessed using RECIST v1.0. The secondary end points were disease control rate (CR + PR + SD), progression free survival (PFS), overall survival (OS), and safety of the combined treatment. PFS and OS curves were plotted using the Kaplan-Meier method.
  
  
  RESULTS
  From July 2009 to July 2012, a total of 53 untreated patients were provisionally registered, and 51 patients were finally registered. Rate of Response to the combined therapy of sorafenib plus IFN-α was 26.2 % (11/42) (CR 1, PR 10). The median PFS was 10.1 months (95 % CI, 6.4 to 18.5 months), and the median OS has not been reached yet. The combined therapy increased neither the incidence of adverse effects (AE) nor the incidence of unexpected AE. A limitation was that a relatively high number of patients (9 patients) were excluded for eligibility criteria violations.
  
  
  CONCLUSIONS
  Our data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients.
  
  
  BACKGROUND
  UMIN000002466 , 9(th) September, 2009.
authors.affiliation: Department of Urology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. etom@kumamoto-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.affiliation: Department of Urology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. yoshiaki.kawano@gmail.com.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. hiraoyos@gmail.com.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Department of Urology, Hiroshima City Asa Hospital, 2-1-1 Kabeminami, Asa, Kita-ku, Hiroshima, 731-0293, Japan. mita@plum.ocn.ne.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Mita
authors.affiliation: Department of Urology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. yarai@uro.med.tohoku.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Urology, Sapporo Medical University, S1 W17, Chuo-ku, Sapporo, 060-8556, Japan. taijit@sapmed.ac.jp.
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.affiliation: Department of Urology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-chou, Matsuyama, 791-0280, Japan. khashine@shikoku-cc.go.jp.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hashine
authors.affiliation: Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. matsua@hiroshima-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Matsubara
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan. tomof@iwate-med.ac.jp.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan. gokimura@nms.ac.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.affiliation: Department of Urology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan. nozomis@mbj.nifty.com.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. ktatsu@uro.med.kyushu-u.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.affiliation: Department of Phamacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida-Konoe-sho, Sakyo-ku, Kyoto, 606-8501, Japan. hinotsus@cc.okayama-u.ac.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Hinotsu
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. naito@uro.med.kyushu-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib