PMID- 24560330 OWN - NLM STAT- MEDLINE DCOM- 20151102 LR - 20220321 IS - 1873-7560 (Electronic) IS - 0302-2838 (Print) IS - 0302-2838 (Linking) VI - 66 IP - 5 DP - 2014 Nov TI - Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma. PG - 874-80 LID - S0302-2838(14)00114-6 [pii] LID - 10.1016/j.eururo.2014.01.035 [doi] AB - 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). DESIGN, SETTING, AND PARTICIPANTS: This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible. INTERVENTION: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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). RESULTS AND LIMITATIONS: 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. PATIENT SUMMARY: 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. TRIAL REGISTRATION: This clinical trial was registered with clinicaltrials.gov (NCT01263769). CI - Copyright (c) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. FAU - Karam, Jose A AU - Karam JA AD - Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Devine, Catherine E AU - Devine CE AD - Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Urbauer, Diana L AU - Urbauer DL AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Lozano, Marisa AU - Lozano M AD - Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Maity, Tapati AU - Maity T AD - Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ahrar, Kamran AU - Ahrar K AD - Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Tamboli, Pheroze AU - Tamboli P AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Tannir, Nizar M AU - Tannir NM AD - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Wood, Christopher G AU - Wood CG AD - Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: CGWood@mdanderson.org. LA - eng SI - ClinicalTrials.gov/NCT01263769 GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140207 PL - Switzerland TA - Eur Urol JT - European urology JID - 7512719 RN - 0 (Antineoplastic Agents) RN - 0 (Imidazoles) RN - 0 (Indazoles) RN - 0 (Protein Kinase Inhibitors) RN - C9LVQ0YUXG (Axitinib) SB - IM CIN - Eur Urol. 2014 Nov;66(5):881-3. PMID: 24631407 CIN - Eur Urol. 2015 Aug;68(2):336. PMID: 26149726 MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Axitinib MH - Biopsy MH - Carcinoma, Renal Cell/diagnostic imaging/*drug therapy/pathology MH - Chemotherapy, Adjuvant MH - Drug Administration Schedule MH - Female MH - Humans MH - Imidazoles/*administration & dosage/adverse effects MH - Indazoles/*administration & dosage/adverse effects MH - Kidney Neoplasms/diagnostic imaging/*drug therapy/pathology MH - *Laparoscopy/methods MH - Male MH - Middle Aged MH - *Neoadjuvant Therapy MH - Neoplasm Staging MH - *Nephrectomy/methods MH - Prospective Studies MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects MH - Quality of Life MH - Texas MH - Time Factors MH - Tomography, X-Ray Computed MH - Treatment Outcome MH - Tumor Burden PMC - PMC4396847 MID - NIHMS671175 OTO - NOTNLM OT - Clinical trial OT - Clinically localized OT - Neoadjuvant OT - Renal cell carcinoma OT - Targeted therapy EDAT- 2014/02/25 06:00 MHDA- 2015/11/03 06:00 PMCR- 2015/11/01 CRDT- 2014/02/25 06:00 PHST- 2013/12/18 00:00 [received] PHST- 2014/01/28 00:00 [accepted] PHST- 2014/02/25 06:00 [entrez] PHST- 2014/02/25 06:00 [pubmed] PHST- 2015/11/03 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - S0302-2838(14)00114-6 [pii] AID - 10.1016/j.eururo.2014.01.035 [doi] PST - ppublish SO - Eur Urol. 2014 Nov;66(5):874-80. doi: 10.1016/j.eururo.2014.01.035. Epub 2014 Feb 7.