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

• Published in: BMC cancer 2015-10, Vol.15 (1), p.667-667, Article 667
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer therapies; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Care and treatment; Clinical trials; Complications and side effects; Cytokines; Drug dosages; Ethics; FDA approval; Female; Hospitals; Humans; Interferon-alpha - administration & dosage; Japan; Kaplan-Meier Estimate; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Male; Medical prognosis; Medical research; Medicine; Medicine, Experimental; Metastasis; Middle Aged; Neoplasm Metastasis; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Pharmaceutical industry; Phenylurea Compounds - administration & dosage; Product development; Prognosis; Review boards; Risk factors; Toxicity; Treatment Outcome; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-015-1675-1

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.