title: A prospective randomised phase II trial of thalidomide with carboplatin compared with carboplatin alone as a first-line therapy in women with ovarian cancer, with evaluation of potential surrogate markers of angiogenesis.
abstract: OBJECTIVE
  To compare the safety and efficacy of thalidomide in combination with carboplatin to carboplatin alone as a first-line therapy in women with ovarian cancer and to evaluate the anti-angiogenic effects of thalidomide by measurement of surrogate markers of angiogenesis.
  
  
  METHODS
  Forty patients with Stage IC-IV ovarian cancer were randomly assigned to receive either carboplatin (AUC 7) intravenously every four weeks for up to six doses (n = 20) or carboplatin at the same dose and schedule, plus thalidomide 100 mg orally daily for six months (n = 20).
  
  
  RESULTS
  After median follow-up of 1.95 years, there was no difference in the overall response rate (90% in carboplatin arm, 75% in combination arm; p = 0.41). Increased incidence of symptoms of constipation, dizziness, tiredness and peripheral neuropathy was observed in the combination arm. There was a significant fall in CA-125 and E-selectin in both arms after treatment and VCAM-1 in the carboplatin arm. No significant difference between the two arms was observed in any of the markers analysed.
  
  
  CONCLUSIONS
  In our trial the addition of thalidomide to carboplatin was well tolerated with no increased efficacy. The fall in some of the angiogenic markers in both groups may reflect tumour response rather than any specific anti-angiogenic effect of thalidomide.
authors.affiliation: Cancer Research UK Medical Oncology Unit, University of Oxford, Churchill Hospital, Oxford.
authors.forename: S R
authors.initials: SR
authors.lastname: Muthuramalingam
authors.forename: J P
authors.initials: JP
authors.lastname: Braybrooke
authors.forename: A D
authors.initials: AD
authors.lastname: Blann
authors.forename: S
authors.initials: S
authors.lastname: Madhusudan
authors.forename: S
authors.initials: S
authors.lastname: Wilner
authors.forename: A
authors.initials: A
authors.lastname: Jenkins
authors.forename: C
authors.initials: C
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Kaur
authors.forename: T
authors.initials: T
authors.lastname: Perren
authors.forename: T S
authors.initials: TS
authors.lastname: Ganesan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy*; D019040:E-Selectin / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D018394:CA-125 Antigen; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D013792:Thalidomide; D016190:Carboplatin