TY - JOUR
T1 - Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan
AU - and Japan RCC Trialist Collaborative Group (JRTCG) investigators
AU - Eto, Masatoshi
AU - Kawano, Yoshiaki
AU - Hirao, Yoshihiko
AU - Mita, Koji
AU - Arai, Yoichi
AU - Tsukamoto, Taiji
AU - Hashine, Katsuyoshi
AU - Matsubara, Akio
AU - Fujioka, Tomoaki
AU - Kimura, Go
AU - Shinohara, Nobuo
AU - Tatsugami, Katsunori
AU - Hinotsu, Shiro
AU - Naito, Seiji
N1 - Funding Information:
This study was supported in part by a grant of The Clinical Research Promotion Foundation.
Funding Information:
M Eto received honoraria from Bayer, Dainippon Sumitomo Pharma, Pfizer, Novartis, Otsuka Pharmaceutical, Shionogi, Ono Pharmaceutical and GlaxoSmithKline, and research funding from Pfizer and Novartis, and fees for promotional materials from Bayer, Pfizer and GlaxoSmithKline. T Tsukamoto received honoraria from Bayer, Dainippon Sumitomo Pharma, Pfizer, Novartis, Otsuka Pharmaceutical, Shionogi and GlaxoSmithKline. G Kimura received honoraria from Pfizer, Bayer, Novartis, Ono Pharmaceutical and GlaxoSmithKline. N Shinohara received honoraria from Bayer, Dainippon Sumitomo Pharma, Pfizer, Novartis, Otsuka Pharmaceutical, Ono Pharmaceutical and GlaxoSmithKline. S Hinotsu received honoraria from Novartis and research funding from Dainippon Sumitomo Pharma. S Naito received honoraria from Pfizer, Bayer, Novartis, Ono Pharmaceutical and GlaxoSmithKline, research funding from Novartis, and fees for promotional materials from Bayer and GlaxoSmithKline.
Publisher Copyright:
© 2015 Eto et al.
PY - 2015/10/9
Y1 - 2015/10/9
N2 - 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)-aα 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-aα 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-aα (3 dosages of 3 million U per week) for 2 weeks. Only IFN-aα-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-aα 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-aα 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. Conclusion: Our data have demonstrated that sorafenib plus IFN-aα treatment is safe and effective for untreated mRCC patients. Trial registration:UMIN000002466 , 9th September, 2009
AB - 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)-aα 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-aα 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-aα (3 dosages of 3 million U per week) for 2 weeks. Only IFN-aα-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-aα 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-aα 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. Conclusion: Our data have demonstrated that sorafenib plus IFN-aα treatment is safe and effective for untreated mRCC patients. Trial registration:UMIN000002466 , 9th September, 2009
KW - Interferon-alpha
KW - Renal cell carcinoma
KW - Sorafenib
UR - http://www.scopus.com/inward/record.url?scp=84943818598&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943818598&partnerID=8YFLogxK
U2 - 10.1186/s12885-015-1675-1
DO - 10.1186/s12885-015-1675-1
M3 - Article
C2 - 26452347
AN - SCOPUS:84943818598
VL - 15
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 667
ER -
