Abstract
OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 923-926 |
| Number of pages | 4 |
| Journal | Urology |
| Volume | 76 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2010 |
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- Urology
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Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial. / Twardowski, Przemyslaw; Stadler, Walter M.; Frankel, Paul; Lara, Primo N; Ruel, Christopher; Chatta, Gurkamal; Heath, Elisabeth; Quinn, David I.; Gandara, David R.
In: Urology, Vol. 76, No. 4, 10.2010, p. 923-926.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase II study of aflibercept (VEGF-Trap) in patients with recurrent or metastatic urothelial cancer, a california cancer consortium trial
AU - Twardowski, Przemyslaw
AU - Stadler, Walter M.
AU - Frankel, Paul
AU - Lara, Primo N
AU - Ruel, Christopher
AU - Chatta, Gurkamal
AU - Heath, Elisabeth
AU - Quinn, David I.
AU - Gandara, David R
PY - 2010/10
Y1 - 2010/10
N2 - OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.
AB - OBJECTIVES: To determine whether aflibercept, a recombinant fusion protein that binds and neutralizes multiple vascular endothelial growth factor isoforms, is effective in the treatment of urothelial cancer. The efficacy of systemic therapies for advanced urothelial cancer after failure of front-line platinum-based chemotherapy is limited. Evidence has shown that vascular endothelial growth factor is important in the pathophysiology of urothelial cancer. METHODS: Patients with measurable, metastatic, or locally advanced urothelial cancer previously treated with 1 platinum-containing regimen were enrolled. Aflibercept was administered at 4 mg/kg intravenously every 2 weeks. The response rate (RR) and progression-free survival (PFS) were assessed in a 2-stage accrual design (22 + 18). A maximum of 40 patients were to be accrued to rule out a null hypothesis RR of 4% and PFS of 3 months versus an alternative RR of 15% and PFS of 5.4 months, with α = 0.12 and β = 0.19. RESULTS: A total of 22 patients were accrued. One partial response (4.5% RR, 95% confidence interval 0.1%-22.8%) was seen. The median PFS was 2.79 months (95% confidence interval 1.74-3.88). Attributable Grade 3 toxicities included fatigue, hypertension, proteinuria, pulmonary hemorrhage, pain, hyponatremia, anorexia, and lymphopenia. No treatment-related Grade 4 or greater toxicities occurred. CONCLUSIONS: Aflibercept was well tolerated, with toxicity similar to those seen with other vascular endothelial growth factor pathway inhibitors; however, it had limited single-agent activity in patients with urothelial carcinoma previously treated with platinum-containing chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=77957756488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957756488&partnerID=8YFLogxK
U2 - 10.1016/j.urology.2010.04.025
DO - 10.1016/j.urology.2010.04.025
M3 - Article
C2 - 20646741
AN - SCOPUS:77957756488
VL - 76
SP - 923
EP - 926
JO - Urology
JF - Urology
SN - 1527-9995
IS - 4
ER -