title: Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood.
authors.forename: M
authors.initials: M
authors.lastname: Zweifel
authors.affiliation: School of Cancer and Enabling Sciences, University of Manchester & Christie Hospital, Manchester.
authors.forename: G C
authors.initials: GC
authors.lastname: Jayson
authors.affiliation: Beatson Oncology Centre, Western Infirmary, Glasgow.
authors.forename: N S
authors.initials: NS
authors.lastname: Reed
authors.affiliation: Dorset Cancer Centre, Poole Hospital NHS Foundation Trust, Poole.
authors.forename: R
authors.initials: R
authors.lastname: Osborne
authors.affiliation: Department of Medical Oncology, Churchill Hospital, Oxford.
authors.forename: B
authors.initials: B
authors.lastname: Hassan
authors.affiliation: UCL Cancer Institute, Cancer Research UK & University College of London Cancer Trials Centre, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ledermann
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood.
authors.forename: G
authors.initials: G
authors.lastname: Shreeves
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood.
authors.forename: L
authors.initials: L
authors.lastname: Poupard
authors.affiliation: OXiGENE Inc., San Francisco, USA.
authors.forename: S-P
authors.initials: SP
authors.lastname: Lu
authors.affiliation: OXiGENE Inc., San Francisco, USA.
authors.forename: J
authors.initials: J
authors.lastname: Balkissoon
authors.affiliation: OXiGENE Inc., San Francisco, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Chaplin
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood. Electronic address: grustin@nhs.net.
authors.forename: G J S
authors.initials: GJS
authors.lastname: Rustin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013267:Stilbenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D013267:Stilbenes; D016190:Carboplatin; C058728:fosbretabulin; D017239:Paclitaxel