Tyrosine kinase inhibitors - A review on pharmacology, metabolism and side effects

Current Drug Metabolism

Volumn 10, Issue 5, 2009, Pages 470-481

  Hartmann, Jörg Thomas ^a   Haap, Michael ^a   Kopp, Hans Georg ^a   Lipp, Hans Peter ^b  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b Department of Endocrinology Metabolism Nephrology Clinical Chemistry and Vascular Medicine ^*  (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTACID AGENT; ANTICONVULSIVE AGENT; CAPECITABINE; CARBAMAZEPINE; CYCLOSPORIN A; CYTOTOXIC AGENT; DASATINIB; ERLOTINIB; FAMOTIDINE; GEFITINIB; GEMCITABINE; GLUCOCORTICOID; IMATINIB; KETOCONAZOLE; LANSOPRAZOLE; LAPATINIB; NILOTINIB; PAZOPANIB; PHENYTOIN; PREDNISONE; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RIFAMPICIN; RIFAMYCIN; SIMVASTATIN; SORAFENIB; SUNITINIB; TRICYCLIC ANTIDEPRESSANT AGENT; TYCERB; UNCLASSIFIED DRUG; UNINDEXED DRUG; WARFARIN; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE;

ACNE; ACUTE LYMPHOBLASTIC LEUKEMIA; ALOPECIA; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; BLEEDING; BONE MARROW SUPPRESSION; BRAIN METASTASIS; BREAST CANCER; CARDIOTOXICITY; CHRONIC MYELOID LEUKEMIA; CONGESTIVE HEART FAILURE; CORNEA PERFORATION; COUGHING; CREATINE KINASE BLOOD LEVEL; DEPIGMENTATION; DERMATITIS; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG SOLUBILITY; DRUG TOLERABILITY; DRUG TRANSPORT; DRUG WITHDRAWAL; DYSPNEA; EDEMA; EPISTAXIS; EYELID EDEMA; FATIGUE; FEVER; FOLLICULITIS; GASTROINTESTINAL STROMAL TUMOR; HEADACHE; HEART FAILURE; HEART INFARCTION; HEMATOLOGIC DISEASE; HEMOGLOBIN BLOOD LEVEL; HEPATITIS; HUMAN; HYPERGLYCEMIA; HYPERICUM PERFORATUM; HYPERTENSION; HYPOCALCEMIA; HYPOGLYCEMIA; HYPOPHOSPHATEMIA; HYPOPIGMENTATION; HYPOTHYROIDISM; HYPOXEMIA; KERATOCONJUNCTIVITIS SICCA; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LIVER DISEASE; LOW DRUG DOSE; LUNG EDEMA; LUNG FIBROSIS; LUNG NON SMALL CELL CANCER; LUNG TOXICITY; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NEPHROTOXICITY; NEUTROPENIA; NONHUMAN; OPTIMAL DRUG DOSE; OSTEOMALACIA; PANCREAS CANCER; PANNICULITIS; PARONYCHIA; PERICARDIAL EFFUSION; PERIORBITAL EDEMA; PERIPHERAL EDEMA; PLEURA EFFUSION; PROTEINURIA; PUSTULE; QT PROLONGATION; RASH; RECOMMENDED DRUG DOSE; RENOVASCULAR HYPERTENSION; REVIEW; SIDE EFFECT; SKIN FISSURE; SKIN INFLAMMATION; SKIN MANIFESTATION; SKIN TOXICITY; STOMATITIS; THROMBOCYTOPENIA; THYROID FUNCTION TEST; TORSADE DES POINTES; VOMITING; WEIGHT REDUCTION; WOUND HEALING IMPAIRMENT; ANIMAL; BINDING SITE; DRUG ANTAGONISM; DRUG DELIVERY SYSTEM; METABOLISM; NEOPLASM; PATHOPHYSIOLOGY;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; DRUG DELIVERY SYSTEMS; HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES;

EID: 70350772288     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009788897975     Document Type: Review

References (89)

1. Beumer, J.H.; Natale, J.J.; Lagattuta, T.F.; Raptis, A.; Egorin, M.J. Disposition of imatinib and its metabolite CGP74588 in a patient with chronic myelogenous leukemia and short-bowel syndrome. Pharmacotherapy, 2006, 26, 903-907.
2. Dutreix, C.; Peng, B.; Mehring, G.; Hayes, M.; Capdeville, R.; Pokorny, R.; Seiberling, M. Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects. Cancer Chemother. Pharmacol., 2004, 54, 290-294. (Pubitemid 39304422)
3. Fausel, C.A. Novel treatment strategies for chronic myeloid leukemia. Am. J. Health Syst. Pharm., 2006, 63, S15-S20. (Pubitemid 44846181)
4. Garcia-Manero, G.; Faderl, S.; O'Brien, S.; Cortes, J.; Talpaz, M.; Kantarjian, H.M. Chronic myelogenous leukemia: a review and update of therapeutic strategies. Cancer, 2003, 98, 437-457. (Pubitemid 36885983)
5. Schleyer, E.; Ottmann, O.G.; Illmer, T.; Pursche, S.; Leopold, T.; Bonin, M.; Freiberg-Richter, J.; Jenke, A.; Platzbecker, U.; Bornhaeuser, M.; Ehninger, G.; Le Coutre, P. Pharmakokinetik von Imatinib (STI571) und seinem Hauptmetaboliten N-Desmethyl-Imatinib. Tumordiagn. Ther., 2004, 25, 192-196.
6. Pappas, P.; Karavasilis, V.; Briasoulis, E.; Pavlidis, N.; Marselos, M. Pharmacokinetics of imatinib mesylate in end stage renal disease. A case study. Cancer Chemother. Pharmacol., 2005, 56, 358-360. (Pubitemid 41095398)
7. Bauer, S.; Hagen, V.; Pielken, H.J.; Bojko, P.; Seeber, S.; Schutte, J. Imatinib mesylate therapy in patients with gastrointestinal stromal tumors and impaired liver function. Anticancer Drugs, 2002, 13, 847-849.
8. Ramadori, G.; Fuzesi, L.; Grabbe, E.; Pieler, T.; Armbrust, T. Successful treatment of hepatocellular carcinoma with the tyrosine kinase inhibitor imatinib in a patient with liver cirrhosis. Anticancer Drugs, 2004, 15, 405-409. (Pubitemid 38526766)
9. De Arriba, J.J.; Nerin, C.; Garcia, E.; Gomez-Aldaravi, L.; Vila, B. Severe hemolytic anemia and skin reaction in a patient treated with imatinib. Ann. Oncol., 2003, 14, 962. (Pubitemid 36827216)
10. van Oosterom, A.T.; Judson, I.; Verweij, J.; Stroobants, S.; Donato, D.P.; Dimitrijevic, S.; Martens, M.; Webb, A.; Sciot, R.; Van Glabbeke, M.; Silberman, S.; Nielsen, O.S. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet, 2001, 358, 1421-1423.
11. Lengerke, C.; Brummendorf, T.; Herrlinger, U.; Horger, M.; Kanz, L.; Hartmann, J.T. Transient respiratory failure possibly associated to imatinib. Invest New Drugs, 2005, 23, 137-138.
12. Kerkela, R.; Grazette, L.; Yacobi, R.; Iliescu, C.; Patten, R.; Beahm, C.; Walters, B.; Shevtsov, S.; Pesant, S.; Clubb, F.J.; Rosenzweig, A.; Salomon, R.N.; Van Etten, R.A.; Alroy, J.; Durand, J.B.; Force, T. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med., 2006, 12, 908-916. (Pubitemid 44175142)
13. Atallah, E.; Durand, J.B.; Kantarjian, H.; Cortes, J. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood, 2007, 110, 1233-1237. (Pubitemid 47281421)
14. Rosti, G.; Martinelli, G.; Baccarani, M. In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'. Nat. Med., 2007, 13, 15-16.
15. Atallah, E.; Kantarjian, H.; Cortes, J. In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'. Nat. Med., 2007, 13, 14-16.
16. Hatfield, A.; Owen, S.; Pilot, P.R. In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'. Nat. Med., 2007, 13, 13-16.
17. Esmaeli, B.; Prieto, V.G.; Butler, C.E.; Kim, S.K.; Ahmadi, M.A.; Kantarjian, H.M.; Talpaz, M. Severe periorbital edema secondary to STI571 (Gleevec). Cancer, 2002, 95, 881-887. (Pubitemid 34839681)
18. Berman, E.; Nicolaides, M.; Maki, R.G.; Fleisher, M.; Chanel, S.; Scheu, K.; Wilson, B.A.; Heller, G.; Sauter, N.P. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N. Engl. J. Med., 2006, 354, 2006-2013.
19. Breccia, M.; Muscaritoli, M.; Aversa, Z.; Mandelli, F.; Alimena, G. Imatinib mesylate may improve fasting blood glucose in diabetic Ph+ chronic myelogenous leukemia patients responsive to treatment. J. Clin. Oncol., 2004, 22, 4653-4655. (Pubitemid 41185138)
20. Veneri, D.; Franchini, M.; Bonora, E. Imatinib and regression of type 2 diabetes. N. Engl. J Med., 2005, 352, 1049-1050.
21. Haap, M.; Gallwitz, B.; Thamer, C.; Mussig, K.; Haring, H.U.; Kanz, L.; Hartmann, J.T. Symptomatic hypoglycemia during imatinib mesylate in a non-diabetic female patient with gastrointestinal stromal tumor. J. Endocrinol. Invest., 2007, 30, 688-692. (Pubitemid 350104100)
22. Sneed, T.B.; Kantarjian, H.M.; Talpaz, M.; O'Brien, S.; Rios, M.B.; Bekele, B.N.; Zhou, X.; Resta, D.; Wierda, W.; Faderl, S.; Giles, F.; Cortes, J.E. The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase. Cancer, 2004, 100, 116-121. (Pubitemid 37553546)
23. Kikuchi, S.; Muroi, K.; Takahashi, S.; Kawano-Yamamoto, C.; Takatoku, M.; Miyazato, A.; Nagai, T.; Mori, M.; Komatsu, N.; Ozawa, K. Severe hepatitis and complete molecular response caused by imatinib mesylate: possible association of its serum concentration with clinical outcomes. Leuk. Lymphoma, 2004, 45, 2349-2351. (Pubitemid 39504334)
24. Brouard, M.; Saurat, J.H. Cutaneous reactions to STI571. N. Engl. J. Med., 2001, 345, 618-619.
25. Tsao, A.S.; Kantarjian, H.; Cortes, J.; O'Brien, S.; Talpaz, M. Imatinib mesylate causes hypopigmentation in the skin. Cancer, 2003, 98, 2483-2487. (Pubitemid 37466664)
26. Ugurel, S.; Hildenbrand, R.; Dippel, E.; Hochhaus, A.; Schadendorf, D. Dose-dependent severe cutaneous reactions to imatinib. Br. J. Cancer, 2003, 88, 1157-1159. (Pubitemid 36606326)
27. Sessa, C.; Vigano, L.; Grasselli, G.; Trigo, J.; Marimon, I.; Llado, A.; Locatelli, A.; Ielmini, N.; Marsoni, S.; Gianni, L. Phase I clinical and pharmacological evaluation of the multi-tyrosine kinase inhibitor SU006668 by chronic oral dosing. Eur. J. Cancer, 2006, 42, 171-178.
28. Kajita, T.; Higashi, Y.; Imamura, M.; Maida, C.; Fujii, Y.; Yamamoto, I.; Miyamoto, E. Effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats. J. Pharm. Pharmacol., 2006, 58, 997-1000.
29. Elliott, M.A.; Mesa, R.A.; Tefferi, A. Adverse events after imatinib mesylate therapy. N. Engl. J. Med., 2002, 346, 712-713.
30. O'Hare, T.; Walters, D.K.; Stoffregen, E.P.; Jia, T.; Manley, P.W.; Mestan, J.; Cowan-Jacob, S.W.; Lee, F.Y.; Heinrich, M.C.; Deininger, M.W.; Druker, B.J. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res., 2005, 65, 4500-4505.
31. Talpaz, M.; Shah, N.P.; Kantarjian, H.; Donato, N.; Nicoll, J.; Paquette, R.; Cortes, J.; O'Brien, S.; Nicaise, C.; Bleickardt, E.; Blackwood-Chirchir, M.A.; Iyer, V.; Chen, T.T.; Huang, F.; Decillis, A.P.; Sawyers, C.L. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N. Engl. J. Med., 2006, 354, 2531-2541.
32. Soverini, S.; Martinelli, G.; Colarossi, S.; Gnani, A.; Rondoni, M.; Castagnetti, F.; Paolini, S.; Rosti, G.; Baccarani, M. Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL. Lancet Oncol., 2007, 8, 273-274.
33. Shah, N.P.; Kim, D.W.; Kantarjian, H.M.; Rousselot, P.; Dorlhiac-Llacer, P.E.; Milone, J.H.; Bleickardt, E.; Francis, S.; Hochhaus, A. Dasatinib 50 mg or 70 mg bid compared to 100 mg or 140 mg qd in patients with CML in chronic phase (CP) who are resistant or intolerant to imatinib: one-year result of CA180034. J. Clin. Oncol., 2007, 25, 7004.
34. Assouline, S.; Laneuville, P.; Gambacorti-Passerini, C. Panniculitis during dasatinib therapy for imatinib-resistant chronic myelogenous leukemia. N. Engl. J Med., 2006, 354, 2623-2624.
35. Quintas-Cardama, A.; Kantarjian, H.; Jones, D.; Nicaise, C.; O'Brien, S.; Giles, F.; Talpaz, M.; Cortes, J. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood, 2007, 109, 497-499.
36. Schade, A.E.; Schieven, G.L.; Townsend, R.; Jankowska, A.M.; Susulic, V.; Zhang, R.; Szpurka, H.; Maciejewski, J.P. Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood, 2008, 111, 1366-1377.
37. Kantarjian, H.; Giles, F.; Wunderle, L.; Bhalla, K.; O'Brien, S.; Wassmann, B.; Tanaka, C.; Manley, P.; Rae, P.; Mietlowski, W.; Bochinski, K.; Hochhaus, A.; Griffin, J.D.; Hoelzer, D.; Albitar, M.; Dugan, M.; Cortes, J.; Alland, L.; Ottmann, O.G. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N. Engl. J Med., 2006, 354, 2542-2551.
38. Rosti, G.; Le Coutre, P.; Bhalla, K.; Giles, F.; Ossenkoppele, G.J.; Hochhaus, A.; Gattermann, N.; Haque, A.; Weitzman, A.; Baccarani, M.; Kantarjian, H. A phase II study of nilotinib administered to imatinib resistant and intolerant patients with chronic myelogenous leukemia (CML) in chronic phase (CP). J. Clin. Oncol., 2007, 25, 7007.
39. Deremer, D.L.; Ustun, C.; Natarajan, K. Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clin. Ther., 2008, 30, 1956-1975.
40. Cersosimo, R.J. Gefitinib: a new antineoplastic for advanced nonsmall-cell lung cancer. Am. J Health Syst. Pharm., 2004, 61, 889-898.
41. Hartmann, J.T.; Pintoffl, J.; Kroening, H.; Bokemeyer, C.; Holtmann, M.; Hoehler, T. Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: A Phase I Study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Onkologie, 2008, in press.
42. Baselga, J.; Rischin, D.; Ranson, M.; Calvert, H.; Raymond, E.; Kieback, D.G.; Kaye, S.B.; Gianni, L.; Harris, A.; Bjork, T.; Averbuch, S.D.; Feyereislova, A.; Swaisland, H.; Rojo, F.; Albanell, J. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J. Clin. Oncol., 2002, 20, 4292-4302. (Pubitemid 35266289)
43. Villano, J.L.; Mauer, A.M.; Vokes, E.E. A case study documenting the anticancer activity of ZD1839 (Iressa) in the brain. Ann. Oncol, 2003, 14, 656-658.
44. Inomata, S.; Takahashi, H.; Nagata, M.; Yamada, G.; Shiratori, M.; Tanaka, H.; Satoh, M.; Saitoh, T.; Sato, T.; Abe, S. Acute lung injury as an adverse event of gefitinib. Anticancer Drugs, 2004, 15, 461-467. (Pubitemid 38736943)
45. Inoue, A.; Saijo, Y.; Maemondo, M.; Gomi, K.; Tokue, Y.; Kimura, Y.; Ebina, M.; Kikuchi, T.; Moriya, T.; Nukiwa, T. Severe acute interstitial pneumonia and gefitinib. Lancet, 2003, 361, 137-139. (Pubitemid 36092019)
46. Rabinowits, G.; Herchenhorn, D.; Rabinowits, M.; Weatge, D.; Torres, W. Fatal pulmonary toxicity in a patient treated with gefitinib for non-small cell lung cancer after previous hemolytic-uremic syndrome due to gemcitabine. Anticancer Drugs, 2003, 14, 665-668. (Pubitemid 37297268)
47. Shah, N.T.; Kris, M.G.; Pao, W.; Tyson, L.B.; Pizzo, B.M.; Heinemann, M.H.; Ben Porat, L.; Sachs, D.L.; Heelan, R.T.; Miller, V.A. Practical management of patients with non-small-cell lung cancer treated with gefitinib. J. Clin. Oncol., 2005, 23, 165-174. (Pubitemid 41702635)
48. Veronese, M.L.; Mosenkis, A.; Flaherty, K.T.; Gallagher, M.; Stevenson, J.P.; Townsend, R.R.; O'Dwyer, P.J. Mechanisms of hypertension associated with BAY 43-9006. J. Clin. Oncol., 2006, 24, 1363-1369.
49. Govindan, R.; Behnken, D.; Read, W.; McLeod, H. Wound healing is not impaired by the epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib. Ann. Oncol., 2003, 14, 1330-1331. (Pubitemid 37039065)
50. Kanazawa, S.; Yamaguchi, K.; Kinoshita, Y.; Muramatsu, M.; Komiyama, Y.; Nomura, S. Aspirin reduces adverse effects of gefitinib. Anticancer Drugs, 2006, 17, 423-427. (Pubitemid 44309985)
51. Shepherd, F.A.; Rodrigues, P.J.; Ciuleanu, T.; Tan, E.H.; Hirsh, V.; Thongprasert, S.; Campos, D.; Maoleekoonpiroj, S.; Smylie, M.; Martins, R.; van Kooten, M.; Dediu, M.; Findlay, B.; Tu, D.; Johnston, D.; Bezjak, A.; Clark, G.; Santabarbara, P.; Seymour, L. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med., 2005, 353, 123-132. (Pubitemid 41058344)
52. Moore, M.J.; Goldstein, D.; Hamm, J.; Figer, A.; Hecht, J.R.; Gallinger, S.; Au, H.J.; Murawa, P.; Walde, D.; Wolff, R.A.; Campos, D.; Lim, R.; Ding, K.; Clark, G.; Voskoglou-Nomikos, T.; Ptasynski, M.; Parulekar, W. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol., 2007, 25, 1960-1966. (Pubitemid 46972777)
53. Lai, S.E.; Minnelly, L.; O'Keeffe, P.; Rademaker, A.; Patel, J.; Bennett, C.L.; Lacouture, M.E. Influence of skin color in the development of erlotinib-induced rash: a report from the SERIES Clinic. J. Clin. Oncol., 2007, 25, 9127.
54. Philip, P.A.; Mahoney, M.R.; Allmer, C.; Thomas, J.; Pitot, H.C.; Kim, G.; Donehower, R.C.; Fitch, T.; Picus, J.; Erlichman, C. Phase II study of erlotinib in patients with advanced biliary cancer. J. Clin. Oncol., 2006, 24, 3069-3074. (Pubitemid 46638942)
55. Buie, L.W.; Lindley, C.; Shih, T.; Ewend, M.; Smith, J.K.; Skelton, M.; Kwock, L.; Morris, D.; Tucker, C.; Collichio, F. Plasma pharmacokinetics and cerebrospinal fluid concentrations of erlotinib in high-grade gliomas: a novel, phase I, dose escalation study. J. Clin. Oncol., 2007, 25, 2054.
56. Nelson, M.H.; Dolder, C.R. Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors. Ann. Pharmacother., 2006, 40, 261-269. (Pubitemid 43269856)
57. Terkola, R. Lapatinib ditosylate (Tykerb). Eur. J. Oncol. Pharm., 2007, 1, 13-17.
58. Midgley, R.S.; Kerr, D.J.; Flaherty, K.T.; Stevenson, J.P.; Pratap, S.E.; Koch, K.M.; Smith, D.A.; Versola, M.; Fleming, R.A.; Ward, C.; O'Dwyer, P.J.; Middleton, M.R. A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan. Ann. Oncol, 2007, 18, 2025-2029. (Pubitemid 350286244)
59. GlaxoSmithKline. Tykerb. http://us.gsk.com/products/assets/us-tykerb.pdf, 2008.
60. Larkin, J.M.; Eisen, T. Kinase inhibitors in the treatment of renal cell carcinoma. Crit. Rev. Oncol. Hematol., 2006, 60, 216-226. (Pubitemid 44709619)
61. Motzer, R.J.; Hoosen, S.; Bello, C.L.; Christensen, J.G. Sunitinib malate for the treatment of solid tumours: a review of current clinical data. Expert. Opin. Investig. Drugs, 2006, 15, 553-561.
62. Motzer, R.J.; Hutson, T.E.; Tomczak, P.; Michaelson, M.D.; Bukowski, R.M.; Rixe, O.; Oudard, S.; Negrier, S.; Szczylik, C.; Kim, S.T.; Chen, I.; Bycott, P.W.; Baum, C.M.; Figlin, R.A. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med., 2007, 356, 115-124. (Pubitemid 46089672)
63. Motzer, R.J.; Michaelson, M.D.; Redman, B.G.; Hudes, G.R.; Wilding, G.; Figlin, R.A.; Ginsberg, M.S.; Kim, S.T.; Baum, C.M.; DePrimo, S.E.; Li, J.Z.; Bello, C.L.; Theuer, C.P.; George, D.J.; Rini, B.I. 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., 2006, 24, 16-24. (Pubitemid 46630489)
64. Motzer, R.J.; Rini, B.I.; Bukowski, R.M.; Curti, B.D.; George, D.J.; Hudes, G.R.; Redman, B.G.; Margolin, K.A.; Merchan, J.R.; Wilding, G.; Ginsberg, M.S.; Bacik, J.; Kim, S.T.; Baum, C.M.; Michaelson, M.D. Sunitinib in patients with metastatic renal cell carcinoma. JAMA, 2006, 295, 2516-2524. (Pubitemid 43854967)
65. Bello, C.L.; Sherman, L.; Zhou, J.; Verkh, L.; Smeraglia, J.; Mount, J.; Klamerus, K.J. Effect of food on the pharmacokinetics of sunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase I study in healthy subjects. Anticancer Drugs, 2006, 17, 353-358.
66. de Groot, J.W.; Links, T.P.; van der Graaf, W.T. Tyrosine kinase inhibitors causing hypothyroidism in a patient on levothyroxine. Ann. Oncol, 2006, 17, 1719-1720.
67. George, S.; Blay, J.Y.; Casali, P.G.; le Cesne, A.; Stephenson, P.; DePrimo, S.E.; Harmon, C.S.; Law, C.N.; Morgan, J.A.; Ray-Coquard, I.; Tassell, V.; Cohen, D.P.; Demetri, G.D. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur. J. Cancer, 2009.
68. Houk, B.E.; Bello, C.L.; Kang, D.; Amantea, M. A population pharmacokinetic meta-analysis of sunitinib malate (SU11248) and its primary metabolite (SU12662) in healthy volunteers and oncology patients. Clin. Cancer Res., 2009, 15, 2497-2506.
69. Desar, I.M.; Burger, D.M.; van Hoesel, Q.G.; Beijnen, J.H.; Van Herpen, C.M.; van der Graaf, W.T. Pharmacokinetics of sunitinib in an obese patient with a GIST. Ann. Oncol., 2009, 20, 599-600.
70. Faivre, S.; Delbaldo, C.; Vera, K.; Robert, C.; Lozahic, S.; Lassau, N.; Bello, C.; Deprimo, S.; Brega, N.; Massimini, G.; Armand, J.P.; Scigalla, P.; Raymond, E. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J. Clin. Oncol., 2006, 24, 25-35. (Pubitemid 46630490)
71. Hartmann, J.T.; Kanz, L. Sunitinib causes periodic hair depigmentation due to temporary c-KIT inhibition. Arch. Dermatol., 2008, 144(11): 1525-1526.
72. Demetri, G.D.; van Oosterom, A.T.; Blackstein, M.; Garrett, C.; Shah, M.; Heinrich, M.; McArthur, G.; Judson, I.; Baum, C.M.; Casali, P.G. Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of SU11248 in patients (pts) following failure of imatinib for metastatic GIST. J. Clin. Oncol., 2005, 23, (abstr. 4000).
73. Chu, T.F.; Rupnick, M.A.; Kerkela, R.; Dallabrida, S.M.; Zurakowski, D.; Nguyen, L.; Woulfe, K.; Pravda, E.; Cassiola, F.; Desai, J.; George, S.; Morgan, J.A.; Harris, D.M.; Ismail, N.S.; Chen, J.H.; Schoen, F.J.; Van den Abbeele, A.D.; Demetri, G.D.; Force, T.; Chen, M.H. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet, 2007, 370, 2011-2019. (Pubitemid 350236338)
74. Patel, T.V.; Morgan, J.A.; Demetri, G.D.; George, S.; Maki, R.G.; Quigley, M.; Humphreys, B.D. A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. J. Natl. Cancer Inst., 2008, 100, 282-284.
75. Eremina, V.; Sood, M.; Haigh, J.; Nagy, A.; Lajoie, G.; Ferrara, N.; Gerber, H.P.; Kikkawa, Y.; Miner, J.H.; Quaggin, S.E. Glomerular specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J. Clin. Invest, 2003, 111, 707-716.
76. Maynard, S.E.; Min, J.Y.; Merchan, J.; Lim, K.H.; Li, J.; Mondal, S.; Libermann, T.A.; Morgan, J.P.; Sellke, F.W.; Stillman, I.E.; Epstein, F.H.; Sukhatme, V.P.; Karumanchi, S.A. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J. Clin. Invest, 2003, 111, 649-658.
77. Maynard, S.; Epstein, F.H.; Karumanchi, S.A. Preeclampsia and angiogenic imbalance. Annu. Rev. Med., 2008, 59, 61-78.
78. Kamba, T.; McDonald, D.M. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br. J. Cancer, 2007, 96, 1788-1795. (Pubitemid 46912024)
79. Desai, J.; Yassa, L.; Marqusee, E.; George, S.; Frates, M.C.; Chen, M.H.; Morgan, J.A.; Dychter, S.S.; Larsen, P.R.; Demetri, G.D.; Alexander, E.K. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann. Intern. Med., 2006, 145, 660-664. (Pubitemid 46768841)
80. Rini, B.I.; Tamaskar, I.; Shaheen, P.; Salas, R.; Garcia, J.; Wood, L.; Reddy, S.; Dreicer, R.; Bukowski, R.M. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl. Cancer Inst., 2007, 99, 81-83.
81. Strumberg, D.; Awada, A.; Hirte, H.; Clark, J.W.; Seeber, S.; Piccart, P.; Hofstra, E.; Voliotis, D.; Christensen, O.; Brueckner, A.; Schwartz, B. Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome? Eur. J. Cancer, 2006, 42, 548-556. (Pubitemid 43227936)
82. Hahn, O.; Stadler, W. Sorafenib. Curr. Opin. Oncol., 2006, 18, 615-621.
83. Wu, S.; Chen, J.J.; Kudelka, A.; Lu, J.; Zhu, X. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol., 2008, 9, 117-123.
84. Schmidinger, M.; Vogl, U.M.; Schukro, C.; Bojic, A.; Bojic, M.; Schmidinger, H.; Zielinski, C.C. Cardiac involvement in patients with sorafenib or sunitinib treatment for metastatic renal cell carcinoma. J. Clin. Oncol., 2007, 25, 5110.
85. Tamaskar, I.R.; Unnithan, J.; Garcia, J.A.; Dreicer, R.; Wood, L.; Iochimescu, A.; Bukowski, R.; Rini, B. Thyroid function test (TFT) abnormalities in patients (pts) with metastatic renal cell carcinoma (RCC) treated with sorafenib. J. Clin. Oncol., 2007, 25, 5048.
86. Lathia, C.; Lettieri, J.; Cihon, F.; Gallentine, M.; Radtke, M.; Sundaresan, P. Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother. Pharmacol., 2006, 57, 685-692.
87. Friedlander, M.; Hancock, K.C.; Benigno, B.; Rischin, D.; Messing, M.; Stringer, C.A.; Tay, E.H.; Kathman, S.; Matthys, G.; Lager, J.J. Pazopanib (GW786034) is active in women with advanced epithelial ovarian fallopian tube and peritoneal cancers: initial results of a phase II study. J. Clin. Oncol., 2007, 25, 5561.
88. Hutson, T.E.; Davis, I.D.; Machiels, J.P.; de Souza, P.L.; Hong, B.F.; Rottey, S.; Baker, K.L.; Crofts, T.; Pandite, L.; Figlin, R. Pazopanib (GW786034) is active in metastatic renal cell carcinoma (RCC): interim results of a phase II randomized discontinuation trial (RDT). J. Clin. Oncol., 2007, 25, 5031.
89. Hurwitz, H.; Dowlati, A.; Savage, S.; Fernando, N.; Lasalvia, S.; Whitehead, B.; Suttle, B.; Collins, D.; Ho, P.; Pandite, L. Safety, tolerability and pharmacokinetics of oral administration of GW786034 in pts with solid tumors. J. Clin. Oncol., 2005, 23, 3012.