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Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer

Khasraw, M., Pavlakis, N., McCowatt, S., Underhill, C., Begbie, S., de Souza, P., Boyce, A., Parnis, F., Lim, V., Harvie, R. and Marx, G. 2010, Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer, Annals of oncology, vol. 21, no. 6, pp. 1302-1307, doi: 10.1093/annonc/mdp524.

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Title Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer
Author(s) Khasraw, M.ORCID iD for Khasraw, M. orcid.org/0000-0003-3249-9849
Pavlakis, N.
McCowatt, S.
Underhill, C.
Begbie, S.
de Souza, P.
Boyce, A.
Parnis, F.
Lim, V.
Harvie, R.
Marx, G.
Journal name Annals of oncology
Volume number 21
Issue number 6
Start page 1302
End page 1307
Total pages 6
Publisher Oxford University Press
Place of publication Oxford, England
Publication date 2010-11-16
ISSN 0923-7534
1569-8041
Keyword(s) anti-heparanase
clinical trial
docetaxel
PI-88
prostate cancer
PSA response
Summary 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/m2 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.
Language eng
DOI 10.1093/annonc/mdp524
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2009, The Author
Persistent URL http://hdl.handle.net/10536/DRO/DU:30046493

Document type: Journal Article
Collection: School of Medicine
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