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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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)-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

Original languageEnglish
Article number667
JournalBMC Cancer
Volume15
Issue number1
DOIs
Publication statusPublished - Oct 9 2015
Externally publishedYes

Fingerprint

Phase II Clinical Trials
Renal Cell Carcinoma
Interferon-alpha
Japan
Interferons
Disease-Free Survival
Therapeutics
Survival
sorafenib
Incidence
Multicenter Studies
Prospective Studies
Cytokines
Safety

Keywords

  • Interferon-alpha
  • Renal cell carcinoma
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan. / Eto, Masatoshi; Kawano, Yoshiaki; Hirao, Yoshihiko; Mita, Koji; Arai, Yoichi; Tsukamoto, Taiji; Hashine, Katsuyoshi; Matsubara, Akio; Fujioka, Tomoaki; Kimura, Go; Shinohara, Nobuo; Tatsugami, Katsunori; Hinotsu, Shiro; Naito, Seiji.

In: BMC Cancer, Vol. 15, No. 1, 667, 09.10.2015.

Research output: Contribution to journalArticle

Eto, M, Kawano, Y, Hirao, Y, Mita, K, Arai, Y, Tsukamoto, T, Hashine, K, Matsubara, A, Fujioka, T, Kimura, G, Shinohara, N, Tatsugami, K, Hinotsu, S & Naito, S 2015, 'Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan', BMC Cancer, vol. 15, no. 1, 667. https://doi.org/10.1186/s12885-015-1675-1
Eto, Masatoshi ; Kawano, Yoshiaki ; Hirao, Yoshihiko ; Mita, Koji ; Arai, Yoichi ; Tsukamoto, Taiji ; Hashine, Katsuyoshi ; Matsubara, Akio ; Fujioka, Tomoaki ; Kimura, Go ; Shinohara, Nobuo ; Tatsugami, Katsunori ; Hinotsu, Shiro ; Naito, Seiji. / Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan. In: BMC Cancer. 2015 ; Vol. 15, No. 1.
@article{c51f4747849745b2a5606f7ca45effbb,
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)-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",
keywords = "Interferon-alpha, Renal cell carcinoma, Sorafenib",
author = "Masatoshi Eto and Yoshiaki Kawano and Yoshihiko Hirao and Koji Mita and Yoichi Arai and Taiji Tsukamoto and Katsuyoshi Hashine and Akio Matsubara and Tomoaki Fujioka and Go Kimura and Nobuo Shinohara and Katsunori Tatsugami and Shiro Hinotsu and Seiji Naito",
year = "2015",
month = "10",
day = "9",
doi = "10.1186/s12885-015-1675-1",
language = "English",
volume = "15",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan

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

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 -