Phase II trial of sequential subcutaneous interleukin-2 plus interferon alpha followed by sorafenib in renal cell carcinoma (RCC)
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Immunotherapy (IL-2 and INF-α) was the treatment of choice for advanced renal cell carcinoma (RCC) until antiangiogenic therapy with tyrosin kinase inhibitors was developed in the early 2000s. This clinical trial explored the efficacy and toxicity of sequential treatment of IL-2 plus INF-α followed by sorafenib.
Eligibility criteria included measurable, non-resectable, histologically confirmed predominantly clear cell RCC, no prior systemic treatment, and ECOG PS 0–2. The treatment regimen was a 6-week cycle of subcutaneous IL-2 at 9 × 106 IU on days 1–6 of weeks 1, 2, 4 and 5 plus s.c. INF-α at 6 × 106 IU on days 1, 3 and 5 of weeks 1–6. Responders received 6 additional weeks of this regimen. All patients received oral sorafenib (400 mg bid) after immunotherapy until disease progression. The primary endpoint was progression-free survival.
Forty-one patients were enrolled, median age 57 years. ECOG was 0/1 in 17/20 patients, 35 patients had prior nephrectomy and 18 patients pure clear cell cancer. Median PFS was 7.4 months (95 % CI 6.5–13.1) and OS was 16.6 months (95 % CI not reached). In 36 patients evaluable for response, ORR was 44.4 % and control rate was 94.4 %. Most adverse events (AEs) were Grade 1 or 2 toxicities (84.7 %). During immunotherapy the most common AEs were pyrexia (82.9 %), asthenia (56.1 %) and anorexia (46.3 %), whereas during sorafenib were diarrhoea (48.8 %) and hand–foot syndrome (46.3 %).
A sequential regimen of IL-2 and INF-α followed by sorafenib showed effectiveness and manageable toxicity in patients with advanced RCC.
KeywordsSequential treatment Immunotherapy Sorafenib Renal cell carcinoma
We are grateful to the patients who participated in this trial. Funding for this study was provided by Bayer Hispania S.L.
- 2.Coppin C, Porzsolt F, Awa A et al (2005) Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev 25:CD001425Google Scholar
- 11.Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS. March 31, 2003 (http://ctep.cancer.gov), Publish Date: August 9, 2006
- 12.Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
- 15.Miyake H, Kusuda Y, Harada KI, Sakai I, Fujisawa M (2011) Third-line sunitinib following sequential use of cytokine therapy and sorafenib in Japanese patients with metastatic renal cell carcinoma. Int J Clin Oncol 18 (published ahead of printing)Google Scholar
- 18.Procopio G, Verzoni E, Bracarda S et al (2011) Sorafenib with interleukin-2 vs sorafenib alone in metastatic renal cell carcinoma: the ROSORC trial. Br J Cancer 104:1256–1261Google Scholar
- 20.Escudier B, Porta C, Bono P et al (2012) Patient preference between pazopanib (Paz) and sunitinib (Sun): results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study. Clin Oncol 30, (Suppl; abstr CRA4502)Google Scholar
- 21.Motzer RJ, Nosov D, Eisen T et al (2012). Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: results from a phase III randomized, openlabel, multicenter trial. J Clin Oncol 30(Suppl; abstr 4501)Google Scholar
- 22.Rini BI, Szczylik C, Tannir P et al (2011) AMG 386 in combination with sorafenib in patients (pts) with metastatic renal cell cancer (mRCC): a randomized, double-blind, placebo-controlled, phase II study. J Clin Oncol 29 (Suppl 7, abstr 309)Google Scholar
- 24.Escudier B, Perol D, Ferlay C et al (2010) Can the combination of temsirolimus and bevacizumab improve the treatment of metastatic renal cell carcinoma? Results of the randomised Torava phase II trial. J Clin Oncol 28:155 (abstr 4516)Google Scholar