Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan

BMC Cancer

Research Article

Shiro Hinotsu¹  Yoshiaki Kawano²  Masatoshi Eto²  Seiji Naito³  Katsunori Tatsugami³  Koji Mita⁴  Nobuo Shinohara⁵  Akio Matsubara⁶  Tomoaki Fujioka⁷  Yoshihiko Hirao⁸  Katsuyoshi Hashine⁹  Go Kimura^1,10  Taiji Tsukamoto^1,11  Yoichi Arai^1,12 

[1] Department of Phamacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida-Konoe-sho, Sakyo-ku, 606-8501, Kyoto, Japan;Department of Urology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, 860-8556, Kumamoto, Japan;Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan;Department of Urology, Hiroshima City Asa Hospital, 2-1-1 Kabeminami, Asa, Kita-ku, 731-0293, Hiroshima, Japan;Department of Urology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, 060-8638, Sapporo, Japan;Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan;Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Japan;Department of Urology, Nara Medical University, 840 Shijo-cho, 634-8521, Kashihara, Nara, Japan;Department of Urology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-chou, 791-0280, Matsuyama, Japan;Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602, Tokyo, Japan;Department of Urology, Sapporo Medical University, S1 W17, Chuo-ku, 060-8556, Sapporo, Japan;Department of Urology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 980-8575, Sendai, Japan;

关键词: Sorafenib;    Interferon-alpha;    Renal cell carcinoma;   

DOI  :  10.1186/s12885-015-1675-1

 received in 2014-12-10, accepted in 2015-10-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundTo 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.MethodsIn 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.ResultsFrom 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.ConclusionOur data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients.Trial registrationUMIN000002466, 9th September, 2009

【 授权许可】

CC BY   
© Eto et al. 2015