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)-alpha 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-alpha 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-alpha (3 dosages of 3 million U per week) for 2 weeks. Only IFN-alpha-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-alpha 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-alpha 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-alpha treatment is safe and effective for untreated mRCC patients.