Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4518
© 2006 American Society of Clinical Oncology

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Abstract

Intermittent chemotherapy in metastatic androgen-independent prostate cancer (AIPC): Initial results from ASCENT

Oregon Health & Science University, Portland, OR; Cross Cancer Institute, Edmonton, AB, Canada; Columbia Presbyterian Medical Center, New York, NY; University of Pittsburgh, Pittsburgh, PA; Tom Baker Cancer Center, Calgary, AB, Canada; BC Cancer Agency, Vancouver, BC, Canada; Novacea, Inc., South San Francisco, CA

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Background: Phase III studies document a survival benefit for 10–12 cycles of docetaxel-containing chemotherapy in AIPC. Further management of patients who complete chemotherapy in response status remains ill-defined. Single-institution phase II data suggest that re-treatment with the same regimen after a treatment holiday is feasible in selected patients. This approach was prospectively tested in a multi-institutional trial. Methods: ASCENT was a multi-institution randomized clinical trial designed to compare the activity and safety of weekly DN-101 (45 µg on day 1) plus docetaxel (36 mg/m² iv on day 2 for 3 weeks of a 4-week cycle) to placebo + docetaxel in patients with chemotherapy-naïve metastatic AIPC. ASCENT was the first large trial to prospectively evaluate intermittent chemotherapy. Patients could opt to suspend treatment if they had a confirmed 50% reduction in serum PSA and a serum PSA 4 ng/ml. PSA was monitored every 4 weeks (CT scans every 8 weeks in patients with measurable disease) during the treatment holiday. Treatment was resumed when serum PSA rose by 50% and was 2 ng/ml or for other evidence of disease progression. The study was not powered to compare treatment holiday outcomes between the two arms. Results: 250 patients were randomized 1:1. Overall PSA response rates were: DN-101: 63%, Placebo 52% (p = 0.07). Overall 18% (DN-101: 20%, Placebo: 16%) of patients entered the intermittent chemotherapy. The median duration of the first chemotherapy holiday was 16 weeks (range 4–74+) (DN-101: 15 weeks, Placebo: 16 weeks). Upon resumption of treatment after the first holiday, 50% of patients responded with a 50% reduction in serum PSA from their post-holiday baseline, 35% met criteria for stable PSA for at least 12 weeks, and 15% progressed on therapy. Conclusions: This is the first report of intermittent chemotherapy in AIPC prospectively tested in a large multi-institutional trial. This strategy results in a clinically meaningful duration of chemotherapy holidays and can be offered to a minority (18%) of patients. Upon re-treatment, most patients (85%) again respond or stabilize PSA values.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novacea sanofi-aventis, Novacea Novacea sanofi-aventis sanofi-aventis, Novacea

Abstract presentation from the 2006 ASCO Annual Meeting