Phase II study of interferon-alpha and doxycycline for advanced renal cell carcinoma
- 61 Downloads
Objective: To assess the efficacy and toxicity of the combination of interferon-alpha and doxycycline in patients with metastatic renal cell carcinoma and to assess the effect of this treatment on serum vascular endothelial growth factor (VEGF) levels. Patients and Methods: Seventeen patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and life expectancy greater than 4 months with radiologically evident advanced renal cell carcinoma were enrolled. Eight patients had prior nephrectomy and 10 patients were treated within 4 months of their diagnosis. Treatment consisted of interferon-alpha up to 9 million units subcutaneously three times per week and doxycycline 300 mg orally twice per day for weeks one and three of each four-week cycle. Toxicity was evaluated on a biweekly basis and response on a bimonthly basis. VEGF plasma levels were assessed monthly as a measure of potential antiangiogenic effect. Results: No objective responses were seen. The mean duration of study was 2.6 cycles (range: 0.8–6.0 cycles). Three patients (17%) tolerated therapy and displayed stable disease for greater than four months. Five patients withdrew from study before the first response evaluation. Ten patients experienced grade 2 gastrointestinal toxicity requiring dose reduction of doxycycline. Eight patients experienced grade 2 fatigue requiring dose reduction of interferon. VEGF plasma levels were initially suppressed in patients who demonstrated progressive disease but not in patients with stable disease. Conclusion: This regimen of doxycycline and interferon-alpha was not efficacious as treatment for renal cell carcinoma. Plasma VEGF levels were significantly decreased during the first two cycles of treatment, but this does not correlate with clinical outcome.
Key Wordsrenal cancer interferon angiogenesis VEGF Phase II trial
Unable to display preview. Download preview PDF.
- 3.Eckhardt SG: Angiogenesis inhibitors as cancer therapy. Hospital Practice Jan 15, 1999Google Scholar
- 5.Sasamura H, Takahashe A, Miyao N, Masumori N, Kitamura H, Itoh N, Tsukamoto T: Inhibitory expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma. BJU Int 86: 768–773, 2002Google Scholar
- 13.Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T. Tursz T: Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J of Med 338(18): 1272–1278, 1998CrossRefGoogle Scholar
- 17.Kuenen BC, Tabernero J, Baselga J, Cavalli F, Pfanner E, Conte PF, Seeber S, Madhusudan S, Deplanque G, Huisman H, Scigalla P, Hoekman K, Harris AL: Efficacy and toxicity of the angiogenesis inhibitor SU5416 as a single agent in patients with advanced renal cell carcinoma, melanoma, and soft tissue sarcoma. Clin Cancer Res 9(5): 1648–1655, 2003PubMedGoogle Scholar
- 18.Lara PN Jr, Quinn DI, Margolin K, Meyers FJ, Longmate J, Frankel P, Mack PC, Turrell C, Valk P, Rao J, Buckley P, Wun T, Gosselin R, Galvin I, Gumerlock PH, Lenz HJ, Doroshow JH, Gandara DR: SU5416 plus interferon alpha in advanced renal cell carcinoma: A phase II California Cancer Consortium Study with biological and imaging correlates of angiogenesis inhibition. Clin Cancer Res 9(13): 4772–4781, 2003PubMedGoogle Scholar
- 20.Kuenen BC, Levi M, Meijers JC, Kakkar AK, van Hinsbergh VW. Kostense PJ, Pinedo HM, Hoekman K: Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arteriosclerosis. Thrombosis & Vascular Biology 22(9): 1500–1505, 2002CrossRefGoogle Scholar
- 21.Motzer RJ, Rini BI, Michaelson M, Redman BG, Hudes GR, Wilding G, Bukowski DJ, George ST, Kim C, Baum M: Phase 2 trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma (RCC). ASCO Proc. Abstract 4508, 2005Google Scholar
- 22.Rini B, Rixi R, Bukowski MD, Michaelson G, Wilding G, Hudes O, Bolte H, Steinfeldt S, Reich D, Motzer R: AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). ASCO Proc. Abstract 4509, 2005Google Scholar
- 23.Escudier B, Szczylik C, Eisen T, Stadler WM, Schwartz B, Shan M, Bukowski RM: Randomized Phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). ASCO Proc. Abstract LB4510, 2005Google Scholar
- 24.Gordon MS, Battiato LA, Jones D, Roth BJ, Harrison-Mann B, Fife R, Collins M, Sledge GW: A phase I trial of doxycycline in patients with cancer. ASCO Proc Abstract 794, 1997Google Scholar
- 25.Liang KY, Zeger SL: Longitudinal data analysis using generalized linear models. Biometrika: 13–22, 1986Google Scholar