Molecular basis for sunitinib efficacy and future clinical development

Nature Reviews Drug Discovery

Volumn 6, Issue 9, 2007, Pages 734-745

  Faivre, Sandrine ^a   Demetri, George ^b   Sargent, William ^c   Raymond, Eric ^a  

^a BEAUJON HOSPITAL   (France)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; ALPHA INTERFERON; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BIOLOGICAL MARKER; CAPECITABINE; CARBOPLATIN; CISPLATIN; CYTOCHROME P450 3A4; DOCETAXEL; DRUG METABOLIZING ENZYME; GEFITINIB; GEMCITABINE; IMATINIB; OXINDOL; PACLITAXEL; PEMETREXED; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR; SEMAXANIB; SORAFENIB; SUNITINIB; UNCLASSIFIED DRUG; VASCULOTROPIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ANOREXIA; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER RESISTANCE; CANCER SURGERY; CARCINOGENESIS; CLINICAL TRIAL; COLORECTAL CANCER; CONTINUOUS INFUSION; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FATIGUE; GASTROINTESTINAL STROMAL TUMOR; GASTROINTESTINAL TOXICITY; GENE EXPRESSION; HAND FOOT SYNDROME; HUMAN; HYPERTENSION; IC 50; KIDNEY CANCER; KIDNEY CARCINOMA; LEUKOPENIA; LEWIS CARCINOMA; LIVER CELL CARCINOMA; LUNG CANCER; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; METASTASIS POTENTIAL; MYELOID LEUKEMIA; NAUSEA; NEUROENDOCRINE TUMOR; NEUTROPENIA; NONHUMAN; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; SARCOMA; SKIN DISCOLORATION; SOLID TUMOR; SQUAMOUS CELL CARCINOMA; STOMATITIS; THROMBOCYTOPENIA; UNSPECIFIED SIDE EFFECT; VOMITING;

ANGIOGENESIS INHIBITORS; ANIMALS; CLINICAL TRIALS; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; HUMANS; INDOLES; NEOPLASMS; PROTEIN-TYROSINE KINASES; PYRROLES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 34548316976     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2380     Document Type: Review

References (63)

1. Folkman, J. Tumor angiogenesis: Therapeutic implications. N. Engl. J. Med. 285, 1182-1186 (1971).
2. Folkman, J. What is the evidence that tumors are angiogenesis dependent? J. Natl Cancer Inst. 82, 4-6 (1990).
3. Cherrington, J. M., Strawn, L. M. & Shawver, L. K. New paradigms for the treatment of cancer: The role of anti-angiogenesis agents. Adv. Cancer Res. 79, 1-38 (2000).
4. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100 57-70 (2000).
5. Faivre, S., Djelloul, S. & Raymond, E. New paradigms in anticancer therapy: Targeting multiple signalling pathways with kinase inhibitors. Semin. Oncol. 33, 407-420 (2006).
6. Motzer, R. J. et al. Sunitinib versus interferon α in metastatic renal-cell carcinoma. N. Engl. J. Med. 356, 115-124 (2007).
7. Demetri, G. D. et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomized controlled trial. Lancet 368, 1329-1338 (2006).
8. Humar R., Kiefer, F. N., Berns, H. & Battegay, E. J. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR-)dependent signaling. FASEB J. 16, 771-780 (2002).
9. Lewis, C. & Murdoch, C. Macrophage responses to hypoxia: Implications for tumor progression and anti-cancer therapies. Am. J. Pathol. 167, 627-635 (2005).
10. Hattori, K. et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nature Med. 8, 841-849 (2002).
11. Rehman, J., Li, J., Orschell, C. M. & March, K. L. Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 107, 1164-1169 (2003).
12. Ribatti, D. The involvement of endothelial progenitor cells in tumor angiogenesis. J. Cell. Mol. Med. 8, 294-300 (2004).
13. Hida, K. et al. Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res. 64, 8249-8255 (2004).
14. Hicklin, D. J. & Ellis, L. M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 23, 1-17 (2005).
15. Erber, R. et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 18, 338-340 (2004).
16. Cao, Y. Emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nature Rev. Cancer 5, 735-743 (2005).
17. Condeelis, J. & Pollard, J. W. Macrophages: Obligate partners for tumor cell migration, invasion and metastasis. Cell 124, 263-266 (2006).
18. Adini, A., Kornaga, T., Firoozbakht, F. & Benjamin, L. E. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res. 62, 2749-2752 (2002).
19. Grimshaw, M. J., Naylor, S. & Balkwill, F. R. Endothelin-2 is a hypoxia-induced autocrine survival factor for breast tumor cells. Mol. Cancer Ther. 1, 1273-1281 (2002).
20. Bergers, G. & Benjamin, L. E. Tumorigenesis and the angiogenic switch. Nature Rev. Cancer. 3, 401-410 (2003).
21. Hurwitz, H. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350, 2335-2342 (2004).
22. Mendel, D. B. et al. In vivo antitumor activity of SU11248, 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, 327-337 (2003).
23. Sun, L. et al. Discovery of
24. Osusky, K. L. et al. The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels. Angiogenesis 7, 225-233 (2004).
25. Duensing, A., Heinrich, M. C., Fletcher, C. D. & Fletcher, J. A. Biology of gastrointestinal stromal tumors: KIT mutations and beyond. Cancer Invest. 22, 106-116 (2004).
26. Naoe, T. & Kiyoi, H. Normal and oncogenic FLT3. Cell. Mol. Life Sci. 61, 2932-2938 (2004).
27. Ichihara, M., Murakumo, Y. & Takahashi, M. RET and neuroendocrine tumors. Cancer Lett. 204, 197-211 (2004).
28. Sapi, E. The role of CSF-1 in normal physiology of mammary gland and breast cancer: An update. Exp. Biol. Med. 229, 1-11 (2004).
29. Baratte, S. et al. Quantitation of SU11248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction. J. Chromatogr. A 1024 87-94 (2004).
30. Abrams, T. J. et al. SU11248 inhibits KIT and platelet-derived growth factor receptor β in preclinical models of human small cell lung cancer. Mol. Cancer Ther. 2, 471-478 (2003).
31. Murray, L. J. et al. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin. Exp. Metastasis 20, 757-766 (2003).
32. O'Farrell, A. M. et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101, 3597-3605 (2003).
33. Faivre, S. et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J. Clin. Oncol. 24, 25-35 (2006).
34. Motzer, R. J., Hoosen, S., Bello, C. L. & Christensen, J. G. Sunitinib malate for the treatment of solid tumors: A review of current clinical data. Expert Opin. Investig. Drugs 15, 553-561 (2006).
35. Motzer, R. J. et al. Activity of SU11248, 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, 16-24 (2006).
36. Motzer, R. J. et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295, 2516-2524 (2006).
37. Motzer R. J. et al. Sunitinib versus interferon-α (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mRCC): Updated results and analysis of prognostic factors. J. Clin. Oncol. 25 (Suppl. 18), 5024 (2007).
38. Judson, I. R., et al. Updated results from a Phase III trial of sunitinib in advanced gastrointestinal stromal tumor (GIST). Ann. Oncol. 17 (Suppl. 9), ix162 (2006).
39. Dileo, P. et al. Updated results from a 'treatment-use' trial of sunitinib in advanced gastrointestinal stromal tumor (GIST). Ann. Oncol. 17 (Suppl. 9), ix162 (2006).
40. Miller, K. D. et al. Safety and efficacy of sunitinib malate (SU11248) as second-line therapy in metastatic breast cancer (MBC) patients: Preliminary results from a Phase II study. Eur. J. Cancer Suppl. 3, 113-114 (2005).
41. Kulke, M. et al. Results of a Phase II study with sunitinib malate (SU11248) in patients (pts) with advanced neuroendocrine tumours (NETS). Eur. J. Cancer Suppl. 3, 204 (2005).
42. Socinski, M. A. et al. Efficacy and safety of sunitinib in previously treated, advanced non-small cell lung cancer (NSCLC): preliminary results of a multicenter Phase II trial. J. Clin. Oncol. 24 (Suppl. 18), 7001 (2006).
43. Socinski, M. A. et al. Efficacy and safety of sunitinib in a multicenter Phase II trial of previously treated, advanced non-small cell lung cancer (NSCLC). Ann. Oncol. 17 (Suppl. 9), ix218 (2006).
44. Faivre, S. et al. Assessment of safety and drug-induced tumor necrosis with sunitinib in patients (pts) with unresectable hepatocellular carcinoma (HCC). J. Clin. Oncol. 25 (Suppl. 18), 3546 (2007).
45. Blay, J-Y. et al. Clinical benefit of continuous daily dosing of sunitinib in patients (pts) with advanced gastrointestinal stromal tumor (GIST). Ann. Oncol. 17 (Suppl. 9), ix163 (2006).
46. Escudier, B. et al. Continuous daily administration of sunitinib malate (SU11248) - a Phase II study in patients (pts) with cytokine-refractory metastatic renal cell carcinoma (mRCC). Ann. Oncol. 17 (Suppl. 9), ix144 (2006).
47. Paez, J. G. et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (2004).
48. Debiec-Rychter, M. et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on Phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer. 40, 689-695 (2004).
49. Morimoto, A. M. et al. Gene expression profiling of human colon xenograft tumors following treatment with SU11248, a multitargeted tyrosine kinase inhibitor. Oncogene 23, 1618-1626 (2004).
50. Jubb, A. M, Oates, A. J., Holden, S. & Koeppen, H. Predicting benefits from anti-angiogenic agents in malignancy. Nature Rev. Cancer 6 626-635 (2006).
51. DePrimo, S. et al. The multitargeted kinase inhibitor sunitinib malate (SU11248): Soluble protein biomarkers of pharmacodynamic activity in patients with metastatic renal cell cancer. Eur. J. Cancer. Suppl. 3, 420 (2005).
52. Bello, C. et al. Analysis of circulating biomarkers of sunitinib malate in patients with unresectable neuroendocrine tumors (NET): VEGF, IL-8, and soluble VEGF receptors 2 and 3. J. Clin. Oncol. 24 (Suppl. 18), 4045 (2006).
53. DePrimo, S. E. 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. J. Clin. Oncol. 24 (Suppl. 18), 578 (2006).
54. Norden-Zfoni, A. et al. Circulating endothelial cells and monocytes as markers of sunitinib malate (SU11248) activity in patients with imatinib mesylate-resistant GIST. Eur. J. Cancer Suppl. 3 423 (2005).
55. Van den Abbeele, A. D. et al. FDG-PET imaging demonstrates kinase target inhibition by sunitinib malate (SU11248) in GIST patients resistant to or intolerant of imatinib mesylate. Eur. J. Cancer Suppl. 3, 202-203 (2005).
56. Davis D. W. et al. Receptor tyrosine kinase activity and apoptosis in gastrointestinal stromal tumors: A pharmacodynamic analysis of response to sunitinib malate (SU11248) therapy. Eur. J. Cancer Suppl. 3, 203 (2005).
57. Bukowski R. M. et al. Final results of the randomized Phase III trial of sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis. J. Clin. Oncol. 25 (Suppl. 18), 5023 (2007).
58. Abou-alfa J. K. et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J. Clin. Oncol, 24, 4293-4300 (2006).
59. Casanovas, O., Hickling, D. J., Bergers, G. & Hanahan, D. Drug resistance by evasion of antiangiogenic targeting of VEGF-signaling in late-stage pancreatic islet tumors. Cancer Cell 8, 299-309 (2005).
60. Huang, J. et al. Vascular remodeling tumors that recur during chronic suppression of angiogenesis. Mol. Cancer Res. 2, 36-42 (2004).
61. Ronnen, E. A. et al. A Phase I study of sunitinib malate (SU11248) in combination with gefitinib in patients with metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 24, 4537 (2006).
62. Verhoef, C., de Wilt, J. H. W. & Verheul, H. M. W. Angiogenesis inhibitors: Perspectives for medical, surgical and radiation oncology. Curr. Pharm. Des. 12, 2623-2630 (2006).
63. Raut, C. P. et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J. Clin. Oncol. 24, 2325-2331 (2006).