Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer
| Autor: | S. McCowatt, Gavin Marx, V. Lim, Rozelle Harvie, Craig Underhill, Francis Parnis, Mustafa Khasraw, Nick Pavlakis, P. de Souza, Stephen Begbie, Adam Boyce |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Oncology medicine.medical_specialty Population Oligosaccharides Phases of clinical research Docetaxel Adenocarcinoma urologic and male genital diseases Prostate cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Castration Treatment Failure Neoplasm Metastasis education Aged Glucuronidase Aged 80 and over education.field_of_study Dose-Response Relationship Drug business.industry Prostatic Neoplasms Hematology Middle Aged medicine.disease Chemotherapy regimen Regimen Prostate-specific antigen Taxoids business Febrile neutropenia medicine.drug |
| Zdroj: | Annals of Oncology. 21:1302-1307 |
| ISSN: | 0923-7534 |
| Popis: | Background: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC. Patients and methods: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m 2 dose every three weeks Results: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6–99 weeks) and 1-year survival was 71%. Conclusions: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile. |
| Databáze: | OpenAIRE |
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