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.
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.
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.
Our data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients.
UMIN000002466 , 9(th) September, 2009.
BMC cancer. 2015 Oct 09*** epublish ***
Masatoshi Eto, Yoshiaki Kawano, Yoshihiko Hirao, Koji Mita, Yoichi Arai, Taiji Tsukamoto, Katsuyoshi Hashine, Akio Matsubara, Tomoaki Fujioka, Go Kimura, Nobuo Shinohara, Katsunori Tatsugami, Shiro Hinotsu, Seiji Naito, Japan RCC Trialist Collaborative Group (JRTCG) investigators
Department of Urology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. Department of Urology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. Department of Urology, Hiroshima City Asa Hospital, 2-1-1 Kabeminami, Asa, Kita-ku, Hiroshima, 731-0293, Japan. Department of Urology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. Department of Urology, Sapporo Medical University, S1 W17, Chuo-ku, Sapporo, 060-8556, Japan. Department of Urology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-chou, Matsuyama, 791-0280, Japan. Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan. Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan. Department of Urology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan. Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. Department of Phamacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida-Konoe-sho, Sakyo-ku, Kyoto, 606-8501, Japan. Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.