Phase II study of interferon-alpha and doxycycline for advanced renal cell carcinoma.
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.


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.


CONCLUSIONS
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.
Huie
Michael
M
University of Wisconsin Comprehensive Cancer Center, K6/550 CSC, Madison, WI 53792, USA.
Oettel
Kurt
K
Van Ummersen
Lynn
L
Kim
Kyung Mann
KM
Zhang
Yulin
Y
Staab
Mary Jane
MJ
Horvath
Dottie
D
Marnocha
Rebecca
R
Douglas
Jeff
J
Drezen
Amy
A
Alberti
Dona
D
Wilding
George
G
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004318:Doxycycline / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014839:Vomiting / Q000139:chemically induced; D015431:Weight Loss
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016898:Interferon-alpha; D042461:Vascular Endothelial Growth Factor A; D004318:Doxycycline