title: The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine.
abstract: There is a need for new treatment strategies and prognostic markers for the management of malignant mesothelioma (MM). The activity of thalidomide/cisplatin/gemcitabine (arm A) or thalidomide alone (arm B) was investigated in two parallel phase II studies in patients with advanced MM, using 6 month progression free survival (PFS) as the principal end-point. The predictive role of pre-treatment and 8 week follow-up serum C-reactive protein (CRP), interlukin-6 (IL-6), interlukin-6 soluble receptor (sIL-6R), mesothelin (SMRP) and vascular endothelial growth factor (VEGF) was also assessed. The proportion of patients with stable disease for >6 months was similar in both studies (arm A 35%, arm B 29%) and toxicity was mainly grade I/II. In univariate analyses only pre-treatment VEGF and CRP were correlated with survival. At 8 weeks post treatment, increased survival was found with low (<median) VEGF and CRP compared with high (>median) VEGF and CRP (P<0.05). Change in VEGF over the first 8 weeks of treatment was also predictive for survival (P<0.05). When pre-treatment VEGF was >median, decreasing VEGF was associated with increased survival (P<0.05). In conclusion, thalidomide alone, or in combination with cisplatin/gemcitabine, controlled disease for >6 months in ∼30% of patients. Patients with decreasing VEGF during treatment had longest survival. Pre-treatment VEGF or CRP and early change in VEGF on treatment may predict treatment benefit and should be examined in future studies.
authors.affiliation: Asbestos Diseases Research Institute, Australia.
authors.forename: Steven Chuan-Hao
authors.initials: SC
authors.lastname: Kao
authors.forename: Rozelle
authors.initials: R
authors.lastname: Harvie
authors.forename: Florian
authors.initials: F
authors.lastname: Paturi
authors.forename: Robyn
authors.initials: R
authors.lastname: Taylor
authors.forename: Ross
authors.initials: R
authors.lastname: Davey
authors.forename: Rick
authors.initials: R
authors.lastname: Abraham
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
authors.forename: Gavin
authors.initials: G
authors.lastname: Marx
authors.forename: Martin
authors.initials: M
authors.lastname: Cullen
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kerestes
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D017322:Clinical Trials, Phase II as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D000093542:Gemcitabine
chemical_list: D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D013792:Thalidomide; D002097:C-Reactive Protein; D002945:Cisplatin; D000093542:Gemcitabine