Drug Monographs: Crizotinib and Ruxolitinib

Abstract

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.

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References

Camidge

D.R.

Bang

Kwak

E.L.

Progression-free survival (PFS) from a phase I study of crizotinib (PF-02341066) in patients with ALK-positive non-small cell lung cancer (NSCLC) [abstract 2501]. J Clin Oncol. 2011; 29(18 suppl). http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&xonfID=102&abstractID=76604. Accessed January 17, 2012.

Crino

Kim

Riely

Initial phase II results with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC): PROFILE 1005 [abstract 7514]. J Clin Oncol. 2011; 29(18 suppl). http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=81844. Accessed January 17, 2012.

Gadgeel

S.M.

Bepler

Crizotinib: an anaplastic lymphoma kinase inhibitor. Future Oncol. 2011; 7(8): 947–953.

Gambacorti-Passerini

Messa

Pogliani

E.M.

Crizotinib in anaplastic large-cell lymphoma. N Engl J Med. 2011; 364(8): 775–776.

Kijima

Takeuchi

Tetsumoto

Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer. Cancer Sci. 2011; 102(8): 1602–1604.

Kwak

E.L.

Bang

Y.J.

Camidge

D.R.

Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363(18): 1693–1703.

Alvey

Bello

Pharmacokinetics (PK) of crizotinib (PF-02341066) in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors [abstract e13065]. J Clin Oncol. 2011; 29(18 suppl). http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=84806. Accessed on January 17, 2012.

S.H.

Bazhenova

Camidge

D.R.

Rapid and dramatic radiographic and clinical response to an ALK inhibitor (crizotinib, PF02341066) in an ALK translocation-positive patient with non-small cell lung cancer. J Thorac Oncol. 2010; 5(12): 2044–2046.

S.H.

Kwak

E.L.

Siwak-Tapp

Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol. 2011; 6(5): 942–946.

10.

Pogliani

E.M.

Diilda

Villa

High response rate to crizotinib in advanced, chemoresistant ALK+ lymphoma patients [abstract e18507]. J Clin Oncol. 2011; 29(18 suppl). http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&xonfID=102&abstractID=83569. Accessed on January 17, 2012.

11.

Shaw

A.T.

Yeap

B.Y.

Solomon

B.J.

Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011; 12(11): 1004–1012.

12.

Rodig

S.J.

Shapiro

G.I.

Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases. Curr Opin Investig Drugs. 2010; 11(12): 1477–1490.

13.

Xalkori [package insert]. New York: Pfizer Labs; 2011. http://labeling.pfizer.com/showlabeling.aspx?id=676. Accessed January 17, 2012.

14.

Tefferi

Begna

Hogan

W.J.

Long-term outcome of treatment with ruxolitinib in myelofibrosis [abstract 1752]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/1752?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=0&volume=118&issue=21&resourcetype=HWCIT Accessed January 17, 2012.

15.

Guglielmelli

Pieri

Tagliarico

Treatment with ruxolitinib (INCB018424) induced changes of microrna expression in granulocytes of patients with polycythemia vera and essential thrombocythemia [abstract 3852]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/3852?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=0&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

16.

Harrison

C.N.

Kiladjian

Al-Ali

H.K.

Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF) [abstract LBA6501]. J Clin Oncol. 2011; 29(18 suppl). http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=82446. Accessed January 17, 2012.

17.

Harrison

C.N.

Kiladjian

J.J.

Al-Ali

H.K.

Health-related quality of life and symptoms in myelofibrosis patients treated with ruxolitinib versus best available therapy [abstract 795]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/795?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=0&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

18.

Harrison

C.N.

Kiladjian

J.J.

Gisslinger

Ruxolitinib provides reductions in splenomegaly across subgroups: an analysis of spleen response in the COMFORT-II study [abstract 279]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/279?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=0&volume=118&issue=21&resourcetype=HWQT. Accessed January 17, 2012.

19.

Jakafi [package insert]. Wilmington, DE: Incyte Corporation; 2011. http://www.incyte.com/products/uspi_jakafi.pdf. Accessed Jan 3, 2011.

20.

Mesa

R.A.

Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis. IDrugs. 2010; 13(6): 394–403.

21.

Mesa

R.A.

Verstovsek

Cervantes Comparison of the efficacy of placebo and best available therapy for the treatment of myelofibrosis in the COMFORT studies [abstract 1753]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/1753?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=10&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

22.

Mesa

R.A.

Gotlib

Gupta

Associations between improvements in myelofibrosis (MF) symptoms and quality of life measures with splenomegaly reduction in COMFORT-I: a randomized, double-blind, phase III trial of the JAK1 and JAK2 inhibitor ruxolitinib versus placebo in patients with MF [abstract 3842]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/3842?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=10&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

23.

McMullin

M.F.

Harrison

C.N.

Niederwieser

Anemia and the use of erythropoietic-stimulating agents with ruxolitinib in the COMFORT-II study [abstract 5147]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/5147?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=10&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

24.

Naqvi

Verstovsek

Kantarjian

Ravandi

A potential role of ruxolitinib in leukemia. Expert Opin Investig Drugs. 2011; 20(8): 1159–1166.

25.

Ogama

Mineyame

Yamamoto

Safety and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers: placebo-controlled, double-blind, dose-escalation phase 1 study [abstract 5162]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/5162?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=0&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

26.

Quintás-Cardama

Vaddi

Liu

Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010; 115(15): 3109–3117.

27.

Shilling

A.D.

Nedza

F.M.

Emm

Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus tyrosine kinase 1/2 inhibitor, in humans. Drug Metab Dispos. 2010; 38(11): 2023–2031.

28.

Stein

B.L.

Crispino

J.D.

Moliterno

A.R.

Janus kinase inhibitors: an update on the progress and promise of targeted therapy in the myeloproliferative neoplasms. Curr Opin Oncol. 2011; 23(6): 609–616.

29.

Tefferi

Litzow

M.R.

Pardanani

Long-term outcome of treatment with ruxolitinib in myelofibrosis. N Engl J Med. 2011; 365(15): 1455–1457.

30.

Verstovsek

Kantarjian

Mesa

R.A.

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010; 363(12): 1117–1127.

31.

Verstovsek

Mesa

R.A.

Gotlib

Consistent benefit of ruxolitinib over placebo in spleen volume reduction and symptom improvement across subgroups and overall survival advantage: results from COMFORT-I [abstract 278]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstracty118/21/278?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=0&volume=118&issue=21&resourcetype=HWCrr. Accessed January 17, 2012.

32.

Verstovsek

Estrov

Cortes

J.E.

The MD Anderson Cancer Center (MDACC) experience with ruxolitinib, an oral JAK1 and JAK2 inhibitor, in myelofibrosis: long-term follow-up outcomes of 107 patients from a phase I/II study [abstract 3851]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/3851?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=10&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.

33.

Verstovsek

Mesa

R.A.

Gotlib

Clinical burden and progression of myelofibrosis in a controlled study population of placebo-treated patients (COMFORT-I) [abstract 5146]. Proc Am Soc Hematol. 2011. http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/5146?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Ruxolitinib&searchid=1&FIRSTINDEX=10&volume=118&issue=21&resourcetype=HWCIT. Accessed January 17, 2012.