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Br J Cancer. 2010 Nov 9;103(10):1554-61. doi: 10.1038/sj.bjc.6605941. Epub 2010 Oct 19.

Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor.

Author information

  • 1Peter MacCallum Cancer Centre, Consultant Medical Oncologist, Division of Haematology and Medical Oncology, Chair of GI Clinical Service, Locked Bag 1, A'Beckett Street, Victoria 8006, Australia. Michael.Michael@petermac.org

Abstract

BACKGROUND:

Tumoural interstitial hypertension, possibly modulated by platelet-derived and vascular endothelial growth factor receptors (PDGFR and VEGFR), may mediate resistance to chemotherapy.

METHODS:

Forty-eight patients with advanced solid tumours received oral PDGFR inhibitor CP-868,596 (60-100 mg twice daily (BID)) and docetaxel (75-100 mg m⁻²), or CP-868,596 (60 mg BID), docetaxel (75 mg m⁻²), and VEGFR inhibitor axitinib (5 mg BID).

RESULTS:

The CP-868,596/docetaxel was escalated as above. The CP-868,596/docetaxel/axitinib was not dose escalated because of increased incidence of mucositis-like adverse events (AEs) with concurrent neutropenia relative to that expected for docetaxel. All tested regimens were tolerable, including 100 mg BID CP-868,596 (recommended phase II dose) plus 100 mg m⁻² docetaxel (maximum approved dose). Most treatment-emergent AEs were mild-moderate and reversible, commonly including nausea, diarrhoea, vomiting, constipation, fatigue, and anaemia (CP-868,596/docetaxel), and hypertension, lethargy, diarrhoea, and fatigue (CP-868,596/docetaxel/axitnib). Pharmacokinetics were unaffected by co-administration. Twenty-one patients achieved stable disease, including all seven evaluable on CP-868,596/docetaxel/axitinib. All nine CP-868,596/docetaxel/axitinib patients received therapy for a median of six (range, 3-16) cycles.

CONCLUSIONS:

The CP-868,596/docetaxel was well tolerated, but increased efficacy was not observed. Addition of axitinib delivered greater benefits than expected in the number of patients achieving prolonged stable disease with a moderate increase in AEs.

PMID:
20959830
[PubMed - indexed for MEDLINE]
PMCID:
PMC2990584
Free PMC Article

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