A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension

Clinical Pharmacology and Therapeutics

Volumn 87, Issue 3, 2010, Pages 303-310

  Gomberg Maitland, M ^a   Maitland, M L ^a   Barst, R J ^b   Sugeng, L ^a   Coslet, S ^a   Perrino, T J ^a   Bond, L ^a   Lacouture, M E ^c   Archer, S L ^a   Ratain, M J ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EMOLLIENT AGENT; IMATINIB; LOPERAMIDE; NATRIURETIC FACTOR; PROSTACYCLIN; PROSTANOID; SILDENAFIL; SORAFENIB; UNIPROST; UREA;

ADULT; AGED; ALOPECIA; ANOREXIA; ARTICLE; CANCER PATIENT; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG DOSE ESCALATION; DRUG ERUPTION; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; DRY SKIN; ECHOCARDIOGRAPHY; ELECTROCARDIOGRAPHY; EXERCISE; FEMALE; HAND FOOT SYNDROME; HEMODYNAMICS; HUMAN; HYPOPHOSPHATEMIA; LUNG FUNCTION TEST; MALE; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PULMONARY HYPERTENSION; SKIN MANIFESTATION; UNSPECIFIED SIDE EFFECT;

ADULT; AGED; BENZENESULFONATES; DIARRHEA; DRUG DISCOVERY; DRUG DOSAGE CALCULATIONS; EXANTHEMA; FEMALE; HUMANS; HYPERTENSION, PULMONARY; MALE; MIDDLE AGED; PROTEIN KINASE INHIBITORS; PYRIDINES;

EID: 77149179051     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2009.217     Document Type: Article

References (46)

1. Wagenvoort, C. & Wagenvoort, N. Pathology of Pulmonary Hypertension, 2nd edn. (John Wiley and Sons, New York, 1977).
2. Wagenvoort, C.A. & Mulder, P.G. Thrombotic lesions in primary plexogenic arteriopathy. Similar pathogenesis or complication? Chest 103, 844-849 (1993).
3. Tuder, R.M. et al. Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis. J. Pathol. 195, 367-374 (2001).
4. Chin, K.M. & Rubin, L.J. Pulmonary arterial hypertension. J. Am. Coll. Cardiol. 51, 1527-1538 (2008).
5. Humbert, M. et al. Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. 173, 1023-1030 (2006).
6. Product Pipeline. In: Medical Advertising News 35074 (2004).
7. Maitland, M.L. & Ratain, M.J. Terminal ballistics of kinase inhibitors: there are no magic bullets. Ann. Intern. Med. 145, 702-703 (2006).
8. Bonnet, S. et al. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation 113, 2630-2641 (2006).
9. Giaid, A. & Saleh, D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med., 333; 214-221 (1995).
10. Giaid, A. et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 328; 1732-1739 (1993). (Pubitemid 23170122)
11. Rabinovitch, M. Molecular pathogenesis of pulmonary arterial hypertension. J. Clin. Invest. 118, 2372-2379 (2008).
12. Tuder, R.M. et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am. J. Respir. Crit. Care Med. 159, 1925-1932 (1999).
13. Tuder, R. Plexiform lesions in primary pulmonary hypertension may represent an abnormal form of angiogenesis. Semin. Respir. Crit. Care Med. 15, 207-214 (1994).
14. Lee, S.D., Shroyer, K.R., Markham, N.E., Cool, C.D., Voelkel, N.F. & Tuder, R.M. Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension. J. Clin. Invest. 101, 927-934 (1998).
15. Michelakis, E.D. Spatio-temporal diversity of apoptosis within the vascular wall in pulmonary arterial hypertension: heterogeneous BMP signaling may have therapeutic implications. Circ. Res. 98, 172-175 (2006).
16. Adnot, S. Lessons learned from cancer may help in the treatment of pulmonary hypertension. J. Clin. Invest. 115, 1461-1463 (2005).
17. Adnot, S. & Eddahibi, S. Lessons from oncology to understand and treat pulmonary hypertension. Int. J. Clin. Pract. Suppl. 16, 19-25 (2007).
18. Humbert, M. & Hoeper, M.M. Severe pulmonary arterial hypertension: a forme fruste of cancer? Am. J. Respir. Crit. Care Med. 178, 551-552 (2008).
19. Rai, P.R. et al. The cancer paradigm of severe pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 178, 558-564 (2008).
20. Strumberg, D. et al. Phase I Clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BaY 43-9006 in patients with advanced refractory solid tumors. J. Clin. Oncol. 23, 965-972 (2005).
21. Wilhelm, S.M. et al. BaY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RaF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64, 7099-7109 (2004).
22. Escudier, B. et al.; TaRGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356, 125-134 (2007).
23. Llovet, J.M. et al.; ShaRP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378-390 (2008).
24. Klein, M. et al. Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling. Circulation 118, 2081-2090 (2008).
25. Moreno-Vinasco, L. et al. Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension. Physiol. Genomics 33, 278-291 (2008).
26. Veronese, M.L. et al. Mechanisms of hypertension associated with BaY 43-9006. J. Clin. Oncol. 24, 1363-1369 (2006).
27. Gomberg-Maitland, M., huo, D., Benza, R.L., McLaughlin, V.V., Tapson, V.F. & Barst, R.J. creation of a model comparing 6-minute walk test to metabolic equivalent in evaluating treatment efects in pulmonary arterial hypertension. J. Heart Lung Transplant. 26, 732-738 (2007).
28. Wu, A.H. et al. Biological variation for N-terminal pro-and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure. Am. J. Cardiol. 92; 628-631 (2003).
29. Gomberg-Maitland, M., McLaughlin, V., Gulati, M. & Rich, S. Efficacy and safety of sildenafl added to treprostinil in pulmonary hypertension. Am. J. Cardiol. 96, 1334-1336 (2005).
30. Simonneau, G. et al.; PacES Study Group. Addition of sildenafl to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann. Intern. Med. 149, 521-530 (2008).
31. Frost, A.E. et al. The 6-min walk test (6MW) as an Efficacy endpoint in pulmonary arterial hypertension Clinical trials: demonstration of a ceiling efect. Vascul. Pharmacol. 43; 36-39 (2005).
32. Chu, T.F. et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370, 2011-2019 (2007).
33. Kerkelä, R. et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med. 12, 908-916 (2006).
34. Hoeper, M.M. et al. Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 160, 535-541 (1999).
35. Rosti, G., Martinelli, G. & Baccarani, M. In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'. Nat. Med. 13, 15; author reply 15-15; author reply 16 (2007).
36. Verweij, J. et al. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTc-ISG-aGITG study 62005. Eur. J. Cancer 43, 974-978 (2007).
37. Khakoo, A.Y. et al. heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer 112;2500-2508 (2008).
38. Shuster, S. high-output cardiac failure from skin disease. Lancet 1, 1338-1340 (1963).
39. Rowell, L.B. Control of regional blood fow during dynamic exercise. In: Human Cardiovascular Control (Oxford University Press, New York, Oxford, (1993).
40. Kellogg, D.L. Jr, Zhao, J.L. & Wu, Y. Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo. Am. J. Physiol. Heart Circ. Physiol. 295, h123-h129 (2008).
41. Sigaudo-Roussel, D., Fromy, B. & Saumet, J.L. In vivo vasodilating mechanisms: who's NOS involved? J. Physiol. (Lond.) 586, 689-690 (2008).
42. Gomberg-Maitland, M. Traditional and alternative designs for pulmonary arterial hypertension trials. Proc. Am. Thorac. Soc. 5, 610-616 (2008).
43. Gomberg-Maitland, M., Thenappan, T., Rizvi, K., Chandra, S., Meads, D.M. & McKenna, S.P. United States validation of the cambridge Pulmonary hypertension Outcome Review (caMPhOR). J. Heart Lung Transplant. 27, 124-130 (2008).
44. McKenna, S.P., Doughty, N., Meads, D.M., Doward, L.c. & Pepke-Zaba, J. The cambridge Pulmonary hypertension Outcome Review (caMPhOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Qual. Life Res. 15, 103-115 (2006)
45. ATS statement: guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med. 166, 111-117 (2002).
46. Patterson, J.A., Naughton, J., Pietras, R.J. & Gunnar, R.M. Treadmill exercise in assessment of the functional capacity of patients with cardiac disease. Am. J. Cardiol. 30, 757-762 (1972).