title: Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma.
abstract: BACKGROUND
  Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.
  
  
  METHODS
  This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives.
  
  
  RESULTS
  Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had >10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with ≤10% sarcomatoid histology (P = .04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7).
  
  
  CONCLUSIONS
  These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: M Dror
authors.initials: MD
authors.lastname: Michaelson
authors.affiliation: Kidney Cancer Center, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.affiliation: Department of Medical Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.affiliation: Kidney Cancer Center, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Eliezer M
authors.initials: EM
authors.lastname: Van Allen
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Kara M
authors.initials: KM
authors.lastname: Olivier
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Department of Medical Oncology, Beth-Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.affiliation: Kidney Cancer Center, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D000093542:Gemcitabine
chemical_list: D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D000077210:Sunitinib; D000093542:Gemcitabine
keywords: chemotherapy; poor risk; renal cell carcinoma; sarcomatoid; targeted; vascular endothelial growth factor (VEGF)