Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: A randomised double-blind phase 2 trial

The Lancet Oncology

Volumn 14, Issue 12, 2013, Pages 1233-1242

  Rini, Brian I ^a   Melichar, Bohuslav ^b   Ueda, Takeshi ^c   Grünwald, Viktor ^d   Fishman, Mayer N ^e   Arranz, José A ^f   Bair, Angel H ^g   Pithavala, Yazdi K ^g   Andrews, Glen I ^g   Pavlov, Dmitri ^g   Kim, Sinil ^g   Jonasch, Eric ^h  

^a TAUSSIG CANCER INSTITUTE   (United States)

^b PALACKÝ UNIVERSITY   (Czech Republic)

^c CHIBA CANCER CENTER   (Japan)

^d HANNOVER MEDICAL SCHOOL   (Germany)

^e H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^f HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN   (Spain)

^g PFIZER INC   (United States)

^h UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AXITINIB; HEMOGLOBIN; PLACEBO;

ABDOMINAL PAIN; ADULT; AGED; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BACKACHE; BODY WEIGHT; CANCER GROWTH; CANCER SURVIVAL; CONSTIPATION; CONTROLLED STUDY; COUGHING; CREATININE BLOOD LEVEL; CZECH REPUBLIC; DECREASED APPETITE; DEHYDRATION; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DYSGEUSIA; DYSPEPSIA; DYSPHONIA; DYSPNEA; ETHNICITY; FATIGUE; FEMALE; GERMANY; GLUCOSE BLOOD LEVEL; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPERTENSION; HYPOTHYROIDISM; JAPAN; KIDNEY METASTASIS; LEG PAIN; LIFE EXPECTANCY; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MUCOSA INFLAMMATION; MULTICENTER STUDY; MUSCULOSKELETAL PAIN; NAUSEA; NEPHRECTOMY; NEUTROPHIL COUNT; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL; RASH; RHINOPHARYNGITIS; RUSSIAN FEDERATION; SIDE EFFECT; SPAIN; STOMATITIS; THROMBOCYTE COUNT; THROMBOCYTOPENIA; THYROTROPIN BLOOD LEVEL; TUMOR VOLUME; UNITED STATES; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; EUROPE; FEMALE; HUMANS; IMIDAZOLES; INDAZOLES; JAPAN; KAPLAN-MEIER ESTIMATE; KIDNEY NEOPLASMS; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; PROTEIN KINASE INHIBITORS; TIME FACTORS; TREATMENT OUTCOME; UNITED STATES;

EID: 84886719423     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(13)70464-9     Document Type: Article

References (34)

1. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007, 356:125-134.
2. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007, 356:115-124.
3. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007, 370:2103-2111.
4. Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 2008, 26:5422-5428.
5. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010, 28:1061-1068.
6. Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 2008, 14:7272-7283.
7. Rixe O, Bukowski RM, Michaelson MD, et al. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 2007, 8:975-984.
8. Rini BI, Wilding G, Hudes G, et al. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol 2009, 27:4462-4468.
9. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011, 378:1931-1939.
10. Tomita Y, Uemura H, Fujimoto H, et al. Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy: a phase II study in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. Eur J Cancer 2011, 47:2592-2602.
11. INLYTA (axitinib) prescribing information, (accessed Aug 29, 2013). http://labeling.pfizer.com/ShowLabeling.aspx?id=759.
12. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 2005, 23:5474-5483.
13. Chen Y, Jiang J, Zhang J, et al. A Phase I study to evaluate the pharmacokinetics of axitinib (AG-13736) in healthy Chinese volunteers. Int J Clin Pharmacol Ther 2011, 49:679-687.
14. Rini BI, Grünwald V, Fishman MN, et al. Axitinib for first-line metastatic renal cell carcinoma (mRCC): overall efficacy and pharmacokinetic (PK) analyses from a randomized phase II study. Proc Am Soc Clin Oncol 2012, 30(suppl). abstr 4503.
15. Rini BI, Garrett M, Poland B, et al. Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis. J Clin Pharmacol 2013, 53:491-504.
16. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000, 92:205-216. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United StatesNational Cancer Institute of the United States, National Cancer Institute of CanadaNational Cancer Institute of Canada.
17. Pithavala YK, Chen Y, Toh M, et al. Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy volunteers. Cancer Chemother Pharmacol 2012, 70:103-112.
18. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003, 13:176-181.
19. Rini BI, Schiller JH, Fruehauf JP, et al. Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors. Clin Cancer Res 2011, 17:3841-3849.
20. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised, open-label, phase 3 trial. Lancet Oncol 2013, in press.
21. Rubinstein L, Crowley J, Ivy P, Leblanc M, Sargent D Randomized phase II designs. Clin Cancer Res 2009, 15:1883-1890.
22. Escudier B, Szczylik C, Hutson TE, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 2009, 27:1280-1289.
23. Motzer RJ, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol 2013, published online Sept 9. 10.1200/JCO.2012.47.4940.
24. Amato RJ, Harris P, Dalton M, et al. A phase II trial of intra-patient dose-escalated sorafenib in patients (pts) with metastatic renal cell cancer (MRCC). Proc Am Soc Clin Oncol 2007, 25(suppl). abstr 5026.
25. Amato RJ, Jac J, Harris P, et al. A phase II trial of intra-patient dose escalated-sorafenib in patients (pts) with metastatic renal cell cancer (MRCC). Proc Am Soc Clin Oncol 2008, 26(suppl). abstr 5122.
26. Gore ME, Jones RJ, Ravaud A, et al. Efficacy and safety of intrapatient dose escalation of sorafenib as first-line treatment for metastatic renal cell carcinoma (mRCC). Proc Am Soc Clin Oncol 2011, 29(suppl). abstr 4609.
27. Adjei AA, Christian M, Ivy P Novel designs and end points for phase II clinical trials. Clin Cancer Res 2009, 15:1866-1872.
28. Molina AM, Zhang J, Lin X, et al. Sunitinib objective response (OR) in metastatic renal cell carcinoma (mRCC): analysis of 1,059 patients treated on clinical trials. Proc Am Soc Clin Oncol 2012, 30(suppl). abstr 4542.
29. Gruenwald V, Busch J, Weikert S, Seidel C Tumor shrinkage during VEGF inhibitor therapy as an independent predictor of PFS and OS in renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 2013, 31(suppl). abstr 423.
30. Motzer RJ, Escudier B, Tomczak P, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013, 14:552-562.
31. Rini BI, Cohen DP, Lu DR, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 2011, 103:763-773.
32. Cohen RB, Oudard S Antiangiogenic therapy for advanced renal cell carcinoma: management of treatment-related toxicities. Invest New Drugs 2012, 30:2066-2079.
33. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002, 20:289-296.
34. Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 2009, 27:5794-5799.