Dasatinib in patients with hormone-refractory progressive prostate cancer: A phase II study
2008; Lippincott Williams & Wilkins; Volume: 26; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2008.26.15_suppl.5156
ISSN1527-7755
AutoresE. Y. Yu, George Wilding, Edwin M. Posadas, Mitchell E. Gross, Stéphane Culine, C. Massard, G. R. Hudes, Shinta Cheng, Prashni Paliwal, C. Sternberg,
Tópico(s)Prostate Cancer Treatment and Research
Resumo5156 Background: Dasatinib is an oral tyrosine kinase inhibitor (TKI), targeting BCR-ABL and Src-family kinases, EphA2, c-KIT, and PDGFR-β. Anti-proliferative and anti-osteoclastic activity observed in dasatinib pre-clinical models support the potential of dasatinib as a targeted therapy for prostate cancer. This phase II study investigated the activity of dasatinib in patients (pts) with metastatic hormone refractory prostate cancer (HRPC). Methods: Male pts with progressive metastatic prostate carcinoma, rising PSA while castrate (testosterone < 50 ng/dL), and no prior chemotherapy were eligible. The starting dose of dasatinib was 100 mg BID. Continuation of bisphosphonates was permitted if disease progression occurred while on therapy. For this two-stage Gehan design, the primary endpoint was response rate. Owing to the possible multiple mechanisms of action, this was a composite of PSA and bone scan responses and disease control by RECIST. Urinary N-telopeptide (UNTx) was determined every 4 weeks as a measure of bone metabolism. Results: 46 pts were enrolled. After the first 25 pts, the starting dose was changed to 70 mg BID for improved tolerability. The disease control rate for 15 RECIST- evaluable pts was 67% (10 had stable disease). Of 27 pts with bone scans at 12 weeks, 16 were stable and 1 was improved. Two of 5 pts with ≥ 2 bone scans at 24 weeks had stable disease. An improved PSA doubling time was seen in 29 of 36 pts (80.1%). One of 36 pts with ≥ 2 PSA measurements had a PSA response, which was a decrease from 19.3 to 3.3 ng/mL. Of the 37 pts with evaluable UNTx levels, including those who continued on bisphosphonate therapy, 21 (57%) had a ≥ 35% decrease from baseline. There were 6 grade 1–2 and 1 grade 3 pleural effusions at 70 mg BID, and 10 grade 1–2 effusions at 100 mg BID. Grade 3 leukopenia occurred in 2% of pts. Conclusions: The preliminary clinical activity, as demonstrated by measures of tumor and PSA response, and UNTx, warrants further study in pts with metastatic HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
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