title: Circulating Tumor Cells in a Phase 3 Study of Docetaxel and Prednisone with or without Lenalidomide in Metastatic Castration-resistant Prostate Cancer.
abstract: Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients. Baseline CTCs were <5 cells/7.5ml blood in 87 (42%) patients and ≥5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count ≥5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to ≥5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from ≥5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003).
  
  
  
  Our study in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.
authors: US Oncology Research, Houston, TX, USA; Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. Electronic address: Nicholas.Vogelzang@usoncology.com.
authors: Nicholas J
authors: NJ
authors: Vogelzang
authors: Institut Gustave Roussy, Department of Cancer Medicine, University of Paris Sud, Villejuif, France.
authors: Karim
authors: K
authors: Fizazi
authors: US Oncology Research, Houston, TX, USA; Rocky Mountain Cancer Centers, Aurora, CO, USA.
authors: John M
authors: JM
authors: Burke
authors: Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors: Ronald
authors: R
authors: De Wit
authors: University Hospital del Mar-IMIM, Barcelona, Spain; Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: Joaquim
authors: J
authors: Bellmunt
authors: Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.
authors: Thomas E
authors: TE
authors: Hutson
authors: Oncology Hematology Care, Inc., Cincinnati, OH, USA.
authors: Edward
authors: E
authors: Crane
authors: US Oncology, Cancer Centers of North Carolina, Raleigh, NC, USA.
authors: William R
authors: WR
authors: Berry
authors: Texas Oncology, Austin, TX, USA.
authors: Kevin
authors: K
authors: Doner
authors: Sarah Cannon Research Institute, Nashville, TN, USA.
authors: John D
authors: JD
authors: Hainsworth
authors: Department of Uro-Oncology, Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie, Warsaw, Poland.
authors: Pawel J
authors: PJ
authors: Wiechno
authors: Celgene Corporation, Summit, NJ, USA.
authors: Kejian
authors: K
authors: Liu
authors: Celgene Corporation, Summit, NJ, USA.
authors: Michelle F
authors: MF
authors: Waldman
authors: Celgene Corporation, Summit, NJ, USA.
authors: Anita
authors: A
authors: Gandhi
authors: Celgene Corporation, Summit, NJ, USA.
authors: Debora
authors: D
authors: Barton
authors: Celgene Corporation, Summit, NJ, USA.
authors: Ulf
authors: U
authors: Jungnelius
authors: Celgene Corporation, Summit, NJ, USA.
authors: Abderrahim
authors: A
authors: Fandi
authors: San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy.
authors: Cora N
authors: CN
authors: Sternberg
authors: Yale Cancer Center, Department of Medicine Division of Oncology, New Haven, CT, USA.
authors: Daniel P
authors: DP
authors: Petrylak
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011241:Prednisone / Q000008:administration & dosage*; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D013792:Thalidomide; D000077269:Lenalidomide; D011241:Prednisone
keywords: Circulating tumor cells; Docetaxel; Lenalidomide; Metastatic castration-resistant prostate cancer; Prostate cancer