期刊
ANNALS OF ONCOLOGY
卷 22, 期 9, 页码 2036-2041出版社
ELSEVIER
DOI: 10.1093/annonc/mdq708
关键词
carboplatin; combretastatin; ovarian cancer; paclitaxel; phase II trial; vascular disrupting agent
类别
资金
- Cancer Research United Kingdom
- OXiGENE Inc., San Francisco, CA, USA
Background: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. Patients and methods: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m(2) minimum 18 h before paclitaxel 175 mg/m(2) and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. Results: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade 2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.
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