Sunitinib Malate for the Treatment of Metastatic Renal Cell Carcinoma and Gastrointestinal Stromal Tumors

Clinical Therapeutics

Volumn 29, Issue 7, 2007, Pages 1338-1353

  Adams, Val R ^a   Leggas, Markos ^a  

^a University of Kentucky   (United States)

Author keywords

adverse events; gastro intestinal stromal tumor; renal cell carcinoma; sunitinib; therapeutic use

Indexed keywords

ALPHA INTERFERON; BEVACIZUMAB; CYTOCHROME P450 3A4; DRUG METABOLITE; IMATINIB; INTERLEUKIN 2; KETOCONAZOLE; PLACEBO; RIFAMPICIN; SU 12662; SUNITINIB; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG;

ABDOMINAL INJURY; ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASTHENIA; BLEEDING; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BREAST CANCER; BREAST FEEDING; CANCER SURVIVAL; CLINICAL TRIAL; CREATININE BLOOD LEVEL; DATA BASE; DIARRHEA; DOSE RESPONSE; DRUG ABSORPTION; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG COST; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEVER; FOOD DRUG INTERACTION; GASTROINTESTINAL STROMAL TUMOR; GASTROINTESTINAL TOXICITY; HAND FOOT SYNDROME; HEADACHE; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; HYPERNATREMIA; HYPERTENSION; HYPOKALEMIA; HYPONATREMIA; HYPOTHYROIDISM; KIDNEY CARCINOMA; KIDNEY METASTASIS; LIVER INJURY; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MAXIMUM PLASMA CONCENTRATION; MEDICAL LITERATURE; MUCOSA INFLAMMATION; NEPHROTOXICITY; NEUROENDOCRINE TUMOR; NEUTROPENIA; OMENTUM LESION; PHARMACODYNAMICS; PREGNANCY; PUBLICATION; QUALITY OF LIFE; RASH; RECOMMENDED DRUG DOSE; SIDE EFFECT; SINGLE DRUG DOSE; SKIN DISCOLORATION; SOLID TUMOR; STOMATITIS; STRUCTURE ACTIVITY RELATION; TASTE; THROMBOCYTOPENIA; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION;

AGE FACTORS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, RENAL CELL; CYTOCHROME P-450 ENZYME SYSTEM; FEMALE; GASTROINTESTINAL STROMAL TUMORS; HUMANS; INDOLES; KIDNEY NEOPLASMS; LACTATION; LUNG NEOPLASMS; NEUROENDOCRINE TUMORS; PREGNANCY; PYRROLES; RECEPTOR PROTEIN-TYROSINE KINASES;

EID: 34548310428     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2007.07.022     Document Type: Article

References (58)

1. Schoffski P., Dumez H., Clement P., et al. Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: A review. Ann Oncol 17 (2006) 1185-1196
2. American Cancer Society. Available at:. Cancer facts & figures (2006). http://www.cancer.org/downloads/SWI-/CAFF2006PWSecured.pdf Available at:
3. Coppin C., Porzsolt F., Awa A., et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev 1 (2005) CD001425
4. Patel P., Chaganti R., and Motzer R. Targeted therapy for metastatic renal cell carcinoma. Br J Cancer 94 (2006) 614-619
5. Houk BE, Amantea M, Motzer RJ, et al. Pharmacokinetics (PK) and efficacy ofsunitinib in patients with metastatic renal cell carcinoma (mRCC). Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 4531.
6. Motzer RJ, Rini BI, Michaelson MD, et al. Phase 2 trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma (RCC). Presented at: ASCO Annual Meeting; May 13-17, 2005; Orlando, Fla. Abstract 4508.
7. Sunitinib (2006), New York, NY, Pfizer Inc [package insert]
8. Blanke C., Eisenberg B., and Heinrich M. Epidemiology of GIST. Am J Gastroenterol 100 (2005) 2366
9. Nilsson B., Bumming P., Meis-Kindblom J., et al. Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era-a population-based study in western Sweden. Cancer 103 (2005) 821-829
10. Rubin B., Fletcher J., and Fletcher C. Molecular insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors. Int J Surg Patkol 8 (2002) 5-10
11. Hirota S., Isozaki K., Moriyama Y., et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Sdence 279 (1998) 577-580
12. Dagher R., Cohen M., Williams G., et al. Approval summary: Imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 8 (2002) 3034-3038
13. Tran T., Davila J., and EI-Serag H. The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1458 cases from 1992 to 2000. Am J Gastroenterol 100 (2005) 162-168
14. Blanke CD, Demetri GD, Von Mehren M, et al. Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor (GIST) patients (pts) treated with imatinib mesylate. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 9528.
15. Sun L., Liang C., Shirazian S., et al. Discovery of 5-[5-fluoro-2-oxo-l,2-dihydroin dol-(3Z)-ylidenemethyl]-2,4-dimethyl-1 H- pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem 46 (2003) 1116-1119
16. Hanahan D., and Weinberg I. The hall-marks of cancer. Ceil 100 (2000) 57-70
17. Fukumura D., Xavier R., Sugiura T., et al. Tumor induction of VEGF promoter activity in stromal cells. Cell 94 (1998) 715-725
18. Laird A., Christensen J., Li G., et al. SU6668 inhibits FIk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEBJ 16 (2002) 681-690
19. Plate K., Breier G., Welch H., and Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359 (1992) 845-848
20. Sundberg C., Ljungstrom M., Lind-mark G., et al. Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma. AmJ Pathol 143 (1993) 1377-1388
21. Abrams T., Murray L., Pesenti E., et al. Preclinical evaluation of the tyrosine kinase inhibitor 5Ul1248 as a single agent and in combination with "standard of care" therapeutic agents for the treatment of breast cancer. Mol Cancer Ther 2 (2003) 1011-1021
22. Mendel D., Laird A., Xin X., et al. In vivo antitumor activiW ofSU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: Determination of a pharmacokinetic/ pharmacodynamic relationship. Clin Cancer Res 9 (2003) 327-337
23. O'Farrell A., Foran J., Fiedler W., et al. An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SUI 1248 in acute myeloid leukemia patients. Clin Cancer Res 9 (2003) 5465-5476
24. O'Farrell A., Abrams T., Yuen H., et al. SUl1248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101 (2003) 3597-3605
25. Fiedler W., Serve H., Dohner H., et al. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 105 (2005) 986-993
26. Motzer R., Michaelson M., Redman B., et al. Activity of SUl1248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24 (2006) 16-24
27. Staehler M., Rohrmann K., Haseke N., et al. Targeted agents for the treatment of advanced renal cell carcinoma. Curr Drug Targets 6 (2005) 835-846
28. Cooney M., Remick S., and Vogelzang N. Novel agents for the treatment of advanced kidney cancer. Clin Adv Hematol Oncol 2 (2004) 664-670
29. Rini B., Sosman J., and Motzer R. Therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: Biology, clinical results and future development. BJU Int 96 (2005) 286-290
30. van Spronsen D., de Weijer K., Mulders P., and De Mulder P. Novel treatment strategies in clear-cell metastatic renal cell carcinoma. Anticancer Drugs 16 (2005) 709-717
31. Tuma R. Three molecularly targeted drugs tested in kidney cancer clinical trials. J Nail Cancer Inst 96 (2004) 1270-1271
32. Motzer R., Rini B., Bukowski R., et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295 (2006) 2516-2524
33. Suppiah R, Finke J, Rini BI, et al. T regulatory cells (Treg) in patients with metastatic renal cell carcinoma (mRCC) decrease during sunitinib treatment: Correlations with clinical responses and T helper 1/T helper 2 (Thl/Th2) bias. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 2526.
34. Bello C., Sherman L., Zhou J., et al. Effect of food on the pharmacokinetics ofsunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: Results from a phase I study in healthy subjects. Anticancer Drugs 17 (2006) 353-358
35. Faivre S., Delbaldo C., Vera K., et al. Safety, pharmacokinetic, and anti-tumor activiW of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24 (2006) 25-35
36. Center for Drug Evaluation and Research. Approval package for: Application number NDA 21-938 (GIST), NDA 21-968 (mRCC). Medical review(s)
37. Available at:. http://www.fda.gov/cder/foi/nda/2006/021938_S000_Sutent_MedR.pdf Accessed October 27, 2006
38. Motzer R., Hoosen S., Bello C., and Christensen J. Sunitinib malate for the treatment of solid tumours: A review of current clinical data. Expert Opin Investig Drugs 15 (2006) 553-561
39. Washington C, Eli M, Bello C, et al. The effect of ketoconazole (KETO), a potent CYP3A4 inhibitor, on SU011248 pharmacokinetics (PK) in caucasian and Asian healthy subjects. Presented at: ASCO Annual Meeting; May 31-June 3, 2003; Chicago, III. Abstract 553.
40. Bello C, Houk B, Sherman L, et al. Effect ofriFampin on the pharmacokinetics of SU11248 in healthy volunteers. Presented at: ASCO Annual Meeting; May 13-17, 2005; Orlando, Fla. Abstract 3078.
41. Motzer R., Bacik J., Schwartz L., et al. Prognostic Factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22 (2004) 454-463
42. Therasse P., Arbuck S., Eisenhauer E., et al., for the European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, and National Cancer Institute of Canada. New guidelines to evaluate the response to treatment in solid tumors. J Nail Cancer Inst 92 (2000) 205-21 6
43. Norden-ZFoni A., Desai J., Manola J., et al. Blood-based biomarkers of SUl1248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin Cancer Res 13 (2007) 2643-2650
44. Deprimo SE, Friece C, Huang X, et al. EFFect of treatment with sunitinib malate, a multitargeted tyrosine kinase inhibitor, on circulating plasma levels of VEGF, soluble VEGF receptors 2 and 3, and soluble KIT in patients with metastatic breast cancer. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 578.
45. Rini BI, George DJ, Michaelson MD, et al. Efficacy and safety ofsunitinib malate (SU11 248) in bevacizumab-refractory metastatic renal cell carcinoma (mRCC). Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 4522.44
46. Maki RG, FletcherJA, Heinrich MC, et al. Results from a continuation trial oF SU11248 in patients (pts) with imatinib (IM)-resistant gas- trointestinal stromal tumor (GIST). Presented at: ASCO Annual Meeting; May 13-17, 2005; Orlando, Fla. Abstract 9011.
47. George S, Casali PG, Blay J, et al. Phase II study of sunitinib administered in a continuous daily dosing regimen in patients (pts) with advanced GIST. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 9532.
48. Morgan JA, Garrett CR, Schutte HJ, et al. Sunitinib for patients (pts) with advanced imatinib (IM)-refractory GIST: Early results from a "treatment-use" trial. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 9540.
49. Socinski MA, Novello S, Sanchez JM, et al. Efficacy and safety of suniti-nib in previously treated, advanced non-small cell lung cancer (NSCLC): Preliminary results of a multicenter phase II trial. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 7001.
50. Kulke M, Lenz H J, Meropol NJ, et al. A phase 2 study to evaluate the efficacy and safety oFSU11248 in patients (pts) with unresectable neuroendocrine tumors (NETs). Presented at: ASCO Annual Meeting; May 13-17, 2005; Orlando, Fla. Abstract 4008.
51. Miller KD, Burnstei H J, Elias AD, et al. Phase II study of SUl1248, a multitargeted receptor tyrosine kinase inhibitor (TKI), in patients (pts) with previously treated metastatic breast cancer (MBC). Presented at: ASCO Annual Meeting; May 13-17, 2005; Orlando, Fla. Abstract 563.
52. Motzer R., Hutson T., Tomczak P., et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356 (2007) 115-124
53. Demetri G., van Oosterom A., Garrett C., et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 368 (2006) 1329-1338
54. Casali PG, Garrett CR, Blackstein ME, et al. Updated results from a phase III trial of sunitinib in GIST patients (pts) for whom imatinib (IM) therapy has failed due to resistance or intolerance. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 9513.
55. Janeway KA, Matthews DC, Butrynski JE, et al. Sunitinib treatment of pediatric metastatic GIST after Failure ofimatinib. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 9519.
56. Johnson D., Fehrenbacher L., Novotny W., et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22 (2004) 2184-2191
57. Daly M., Makris A., Reed M., and Lewis C. Hemostatic regulators of tumor angiogenesis: A source of anti-angiogenic agents for cancer treatment?. J Natl Cancer Inst 95 (2003) 1660-1673
58. Shaheen PE, Tamasker IR, Salas RN, et al. Thyroid Function tests (TFTs) abnormalities in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib. Presented at: ASCO Annual Meeting; June 2-6, 2006; Atlanta, Ga. Abstract 4605.