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Prostate Cancer
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DGDispatch
AZD2171 Well Tolerated in Patients with Advanced Prostate Cancer: Presented at AACR-NCI-EORTC
By Maggie Schwarz
PHILADELPHIA, PA -- November 18, 2005 -- Early data on the investigational agent, AZD2171, show the drug has broad-spectrum antitumor activity in a range of xenograft models, consistent with potent inhibition of vascular endothelial growth factor (VEGF) signaling and angiogenesis.
The agent, an oral, selective and reversible inhibitor of VEGF receptor signaling, appears to be generally well tolerated at doses up to 20 mg/day in patients with advanced prostate cancer.
Lead investigator Charles Ryan, Assistant Clinical Professor, University of California, San Francisco, San Francisco, California, United States, presented the findings from an ongoing, phase 1, multicenter, open-label dose escalation trial here on November 16th at the International Conference on Molecular Targets and Cancer Therapeutics.
The conference was organized jointly by the American Association for Cancer Research - National Cancer Institute - European Organisation for Research and Treatment of Cancer (AACR-NCI-EORTC).
The trial was designed to assess the safety and tolerability of AZD2171 in patients with advanced prostate adenocarcinoma.
Dr. Ryan and colleagues recruited 24 patients with advanced prostate carcinoma from three centers in the United States. Patients have received once-daily oral doses of AZD2171 (1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg or 30 mg) in continuous 21-day treatment cycles until a withdrawal criterion is met (disease progression, dose-limiting toxicity or voluntary discontinuation by the patient). No intra-patient dose escalation has occurred.
The researches have determined objective response rate using the Response Evaluation Criteria in Solid Tumors (RECIST) and changes in prostate-specific antigen (PSA) levels.
No objective tumor responses have been observed among the 14 patients with bi-dimensionally measurable disease. Four patients had a RECIST-defined best response of stable disease (10 mg, n = 1; 20 mg, n = 3).
No PSA responses have been observed to date. However, a PSA decline of less than 50% was observed in two patients. The PSA decline ranged from 22% to 36% between cycles 1 and 4 in one patient (20 mg) and was 26% on day 8 of cycle 1 in the second patient (30 mg).
A 30-day follow-up after the termination of treatment showed that one patient in the 20 mg cohort experienced a reduction in PSA levels greater than 50% from baseline. PSA levels increased from 68.14 ng/mL at baseline to 73.89 ng/mL at the time of treatment discontinuation.
However, after 30 days of follow-up, PSA levels declined to 3.28 ng/mL, which was confirmed on repeated testing. Examination of the corresponding CT scan from this patient revealed resolution of retroperitoneal adenopathy. This patient remains free from further disease progression 6 months after stopping treatment and has received no further antitumor therapy.
Dr. Ryan concluded that the PSA changes and off-study objective response are encouraging. He asserted that AZD2171 merits further investigation in the treatment of prostate cancer.
[Presentation title: Phase I Evaluation of AZD2171, a Highly Potent VEGFR Tyrosine Kinase Inhibitor, in Patients with Advanced Prostate Carcinoma. Abstract A4]
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