title: Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma.
abstract: BACKGROUND
  Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery.
  
  
  OBJECTIVE
  To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC).
  
  
  METHODS
  This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible.
  
  
  METHODS
  Patients received axitinib 5mg for up to 12 wk. Axitinib was continued until 36h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy.
  
  
  METHODS
  The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST).
  
  
  CONCLUSIONS
  A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers.
  
  
  CONCLUSIONS
  Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC.
  
  
  RESULTS
  In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use.
  
  
  BACKGROUND
  This clinical trial was registered with clinicaltrials.gov (NCT01263769).
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Devine
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Urbauer
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Lozano
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tapati
authors.initials: T
authors.lastname: Maity
authors.affiliation: Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ahrar
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: CGWood@mdanderson.org.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077784:Axitinib; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010535:Laparoscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D013781:Texas; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib
keywords: Clinical trial; Clinically localized; Neoadjuvant; Renal cell carcinoma; Targeted therapy