title: A Phase II Study of Pazopanib in Patients with Localized Renal Cell Carcinoma to Optimize Preservation of Renal Parenchyma.
abstract: OBJECTIVE
  Preservation of renal function is prioritized during surgical management of localized renal cell carcinoma. VEGF targeted agents can downsize tumors in metastatic renal cell carcinoma and may do the same in localized renal cell carcinoma, allowing for optimal preservation of renal parenchyma associated with partial nephrectomy.
  
  
  METHODS
  Localized clear cell renal cell carcinoma patients meeting 1 or both of the following criteria were enrolled in a prospective phase II trial, including radical or partial nephrectomy likely to yield a glomerular filtration rate of less than 30 ml/minute/1.73 m(2), or partial nephrectomy high risk due to high complexity (R.E.N.A.L. 10 to 12) or tumor adjacent to hilar vessels. Pazopanib (800 mg once daily) was administered for 8 to 16 weeks with repeat imaging at completion of therapy, followed by surgery.
  
  
  RESULTS
  A total of 25 patients enrolled with a median tumor size of 7.3 cm and a median R.E.N.A.L. score of 11. Of index lesions 80% were high complexity and 56% of patients had a solitary kidney. Patients received a median of 8 weeks of pazopanib. The median interval from treatment start to surgery was 10.6 weeks. R.E.N.A.L. score decreased in 71% of tumors and 92% of patients experienced a reduction in tumor volume. Six of 13 patients for whom partial nephrectomy was not possible at baseline were able to undergo partial nephrectomy after treatment. The mean parenchymal volume that could be saved with surgery increased from an estimated 107 to 173 cc (p = 0.0015). In 5 patients a urine leak developed, which was managed conservatively, and 7 received a transfusion, of whom 1 required embolization.
  
  
  CONCLUSIONS
  Neoadjuvant pazopanib resulted in downsizing localized renal cell carcinoma, allowing for improved preservation of renal parenchyma and enabling partial nephrectomy in a select subset of patients who would otherwise require radical nephrectomy.
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio; Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio.
authors: Brian I
authors: BI
authors: Rini
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Elizabeth R
authors: ER
authors: Plimack
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Toshio
authors: T
authors: Takagi
authors: Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio.
authors: Paul
authors: P
authors: Elson
authors: Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio.
authors: Laura S
authors: LS
authors: Wood
authors: Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio.
authors: Robert
authors: R
authors: Dreicer
authors: Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio.
authors: Timothy
authors: T
authors: Gilligan
authors: Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio.
authors: Jorge
authors: J
authors: Garcia
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Zhiling
authors: Z
authors: Zhang
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Jihad
authors: J
authors: Kaouk
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Venkatesh
authors: V
authors: Krishnamurthi
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Andrew J
authors: AJ
authors: Stephenson
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Amr
authors: A
authors: Fergany
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio.
authors: Eric A
authors: EA
authors: Klein
authors: Department of Urology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Robert G
authors: RG
authors: Uzzo
authors: Department of Urology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: David Y T
authors: DY
authors: Chen
authors: Department of Urology, Cleveland Clinic, Cleveland, Ohio. Electronic address: campbes3@ccf.org.
authors: Steven C
authors: SC
authors: Campbell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007191:Indazoles; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods*; D009929:Organ Size; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: carcinoma; kidney; neoadjuvant therapy; nephrectomy; pazopanib; renal cell