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.
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.
Authors: B C Kuenen; M Levi; J C M Meijers; A K Kakkar; V W M van Hinsbergh; P J Kostense; H M Pinedo; K Hoekman Journal: Arterioscler Thromb Vasc Biol Date: 2002-09-01 Impact factor: 8.311
Authors: A Lukkonen; T Sorsa; T Salo; T Tervahartiala; E Koivunen; L Golub; S Simon; U H Stenman Journal: Int J Cancer Date: 2000-05-15 Impact factor: 7.396
Authors: Primo N Lara; David I Quinn; Kim Margolin; Frederick J Meyers; Jeff Longmate; Paul Frankel; Philip C Mack; Corinne Turrell; Peter Valk; Jyotsna Rao; Penelope Buckley; Ted Wun; Robert Gosselin; Irina Galvin; Paul H Gumerlock; Heinz Josef Lenz; James H Doroshow; David R Gandara Journal: Clin Cancer Res Date: 2003-10-15 Impact factor: 12.531
Authors: H Sasamura; A Takahashi; N Miyao; M Yanase; N Masumori; H Kitamura; N Itoh; T Tsukamoto Journal: Br J Cancer Date: 2002-03-04 Impact factor: 7.640