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Wikipedia

Carfilzomib

April 12, 2024

Carfilzomib, sold under the brand name Kyprolis, is an anti-cancer medication acting as a selective proteasome inhibitor. Chemically, it is a tetrapeptide epoxyketone and an analog of epoxomicin.[4] It was developed by Onyx Pharmaceuticals.

Carfilzomib
Clinical data
Trade namesKyprolis
Other namesPX-171-007
AHFS/Drugs.comMonograph
MedlinePlusa612031
License data
Pregnancy
category
  • AU: C
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding97%[3]
MetabolismExtensive; CYP plays a minor role
Identifiers
  • (2S)-4-Methyl-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide
CAS Number
  • 868540-17-4
PubChem CID
  • 11556711
IUPHAR/BPS
  • 7420
DrugBank
  • DB08889
ChemSpider
  • 9731489
UNII
  • 72X6E3J5AR
KEGG
  • D08880
ChEBI
  • CHEBI:65347
ChEMBL
  • ChEMBL451887
CompTox Dashboard (EPA)
  • DTXSID4048690
ECHA InfoCard100.219.957
Chemical and physical data
FormulaC40H57N5O7
Molar mass719.924 g·mol−1
3D model (JSmol)
  • Interactive image
  • O=C(N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)[C@@]1(OC1)C)CC(C)C)Cc2ccccc2)CC(C)C)CCc3ccccc3)CN4CCOCC4
  • InChI=1S/C40H57N5O7/c1-27(2)22-32(36(47)40(5)26-52-40)42-39(50)34(24-30-14-10-7-11-15-30)44-38(49)33(23-28(3)4)43-37(48)31(17-16-29-12-8-6-9-13-29)41-35(46)25-45-18-20-51-21-19-45/h6-15,27-28,31-34H,16-26H2,1-5H3,(H,41,46)(H,42,50)(H,43,48)(H,44,49)/t31-,32-,33-,34-,40+/m0/s1
  • Key:BLMPQMFVWMYDKT-NZTKNTHTSA-N

The US Food and Drug Administration (FDA) approved it in July 2012.[5][6]

Medical uses edit

The FDA approved carfilzomib in July 2012, for use in people with multiple myeloma who have received at least two prior therapies, including treatment with bortezomib and an immunomodulatory therapy (such as lenalidomide) and have demonstrated disease progression on or within 60 days of completion of the last therapy.[5]

Mechanism edit

Carfilzomib covalently [7] irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme that degrades unwanted cellular proteins. Carfilzomib displays minimal interactions with non-proteasomal targets, thereby improving safety profiles over bortezomib.[7] Inhibition of proteasome-mediated proteolysis results in a build-up of polyubiquitinated proteins, which may cause cell cycle arrest, apoptosis, and inhibition of tumor growth.[4]

History edit

Carfilzomib is derived from epoxomicin, a natural product that was shown by the laboratory of Craig Crews at Yale University to inhibit the proteasome.[8] The Crews laboratory subsequently invented a more specific derivative of epoxomicin named YU101,[9] which was licensed to Proteolix, Inc. Scientists at Proteolix invented a new, distinct compound that had potential use as a drug in humans, known as carfilzomib. Proteolix advanced carfilzomib to multiple phase I and II clinical trials, including a pivotal phase 2 clinical trial designed to seek accelerated approval.[10] Clinical trials for carfilzomib continue under Onyx Pharmaceuticals, which acquired Proteolix in 2009.[10]

In January 2011, the FDA granted carfilzomib fast-track status, allowing Onyx to initiate a rolling submission of its new drug application for carfilzomib.[11] In December 2011, the FDA granted Onyx standard review designation,[12][13] for its new drug application submission based on the 003-A1 study, an open-label, single-arm phase IIb trial. The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide.[14]

Initial approval was based on response rate.[5] Data demonstrating an overall survival benefit was demonstrated in the ENDEAVOR trial and approved by the FDA.[15]

Clinical trials & side effects edit

Completed edit

A single-arm, phase II trial (003-A1) of carfilzomib in patients with relapsed and refractory multiple myeloma showed that single-agent carfilzomib demonstrated a clinical benefit rate of 36% in the 266 patients evaluated and had an overall response rate of 22.9% and median duration of response of 7.8 months. The FDA approval of carfilzomib was based on results of the 003-A1 trial.[3]

In a phase II trial (004), carfilzomib had a 53% overall response rate among patients with relapsed and/or refractory multiple myeloma who had not previously received bortezomib. This study also included a bortezomib-treated cohort. Results were reported separately.[16] This study also found prolonged carfilzomib treatment was tolerable, with approximately 22% of patients continuing treatment beyond one year. The 004 trial was a smaller study originally designed to investigate the impact of carfilzomib treatment in relationship to bortezomib treatment in less heavily pretreated (1–3 prior regimens) patients.[17]

A phase II trial (005), which assessed the safety, pharmacokinetics, pharmacodynamics and efficacy of carfilzomib, in patients with multiple myeloma and varying degrees of renal impairment, where nearly 50% of patients were refractory to both bortezomib and lenalidomide, demonstrated that pharmacokinetics and safety were not influenced by the degree of baseline renal impairment. Carfilzomib was tolerable and demonstrated efficacy.[18]

In another phase II trial (006) of patients with relapsed and/or refractory multiple myeloma, carfilzomib in combination with lenalidomide and dexamethasone demonstrated an overall response rate of 69%.[19]

A phase II trial (007) for multiple myeloma and solid tumors showed promising results.[20][21]

In phase II trials of carfilzomib, the most common grade 3 or higher treatment-emergent adverse events were hematologic toxicity [22] with thrombocytopenia, anemia, lymphopenia, neutropenia, pneumonia, fatigue and hyponatremia.[23]

In a frontline phase I/II study, the combination of carfilzomib, lenalidomide, and low-dose dexamethasone was highly active and well tolerated, permitting the use of full doses for an extended time in newly diagnosed multiple myeloma patients, with limited need for dose modification. Responses were rapid and improved over time, reaching 100% very good partial response.[24]

Furthermore, gastrointestinal disturbances, including diarrhea and nausea are non hematologic group of side effects commonly reported with proteasome inhibitors.[22] Additionally, cardiovascular toxicity may be an outcome of carfilzomib treatment due to the effects on proteasomes in the myocardium.[22] Thus, patient evaluation and risk assessment prior to initiation of therapy with carfilzomib is crucial.[25]

ASPIRE trial edit

A phase III confirmatory clinical trial, known as the ASPIRE trial, compared carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma and found improved progression-free survival and overall survival. Treatment discontinuation because of adverse effects occurred less frequently in the KRd arm, and events included thrombocytopenia, hypertension, and heart failure.[26][27]

Society and culture edit

Economics edit

Carfilzomib costs approximately US$10,000 per 28-day cycle.[28]

References edit

  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. ^ "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.
  3. ^ a b c "Kyprolis- carfilzomib injection, powder, lyophilized, for solution". DailyMed. 26 August 2020. Retrieved 13 November 2020.
  4. ^ a b "NCI Drug Dictionary". National Cancer Institute. Retrieved 13 November 2020.
  5. ^ a b c . FDA. 2012-07-20. Archived from the original on 2013-01-28. Retrieved 2013-07-23.
  6. ^ "Drug Approval Package: Kyprolis (carfilzomib) for Injection NDA #202714". U.S. Food and Drug Administration (FDA). 20 August 2012. Retrieved 10 April 2023.
  7. ^ a b Park JE, Park J, Jun Y, Oh Y, Ryoo G, Jeong YS, et al. (May 2019). "Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation". Journal of Controlled Release. 302: 148–159. doi:10.1016/j.jconrel.2019.04.006. PMC 6638563. PMID 30954620.
  8. ^ Meng L, Mohan R, Kwok BH, Elofsson M, Sin N, Crews CM (August 1999). "Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity". Proceedings of the National Academy of Sciences of the United States of America. 96 (18): 10403–8. Bibcode:1999PNAS...9610403M. doi:10.1073/pnas.96.18.10403. PMC 17900. PMID 10468620.
  9. ^ Myung J, Kim KB, Lindsten K, Dantuma NP, Crews CM (February 2001). "Lack of proteasome active site allostery as revealed by subunit-specific inhibitors". Molecular Cell. 7 (2): 411–20. doi:10.1016/S1097-2765(01)00188-5. PMID 11239469.
  10. ^ a b "Carfilzomib: From Discovery To Drug". Chemical & Engineering News. 2012-08-27. Retrieved 2013-07-30.
  11. ^ "Onyx multiple myeloma drug wins FDA fast-track status". San Francisco Business Times. 2011-01-31. Retrieved 2011-09-01.
  12. ^ "Beacon Breaking News – Carfilzomib to Get Standard, Not Priority, FDA Review". The Myeloma Beacon. Retrieved 2012-02-27.
  13. ^ . FDA. Archived from the original on 2012-02-17. Retrieved 2012-02-27.
  14. ^ . ASCO 2011; Abstract 8027. 2011. Archived from the original on 2012-03-23. Retrieved 2011-09-01.
  15. ^ Broderick JM (18 January 2018). "FDA Approves Carfilzomib Label Update in Myeloma". OncLive. Retrieved 10 April 2023.
  16. ^ Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, McDonagh K, et al. (September 2012). "An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib". British Journal of Haematology. 158 (6): 739–48. doi:10.1111/j.1365-2141.2012.09232.x. PMC 5818209. PMID 22845873.
  17. ^ Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, et al. (June 2012). "An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma". Blood. 119 (24): 5661–70. doi:10.1182/blood-2012-03-414359. PMC 4123327. PMID 22555973.
  18. ^ Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, et al. (August 2013). "Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety". Leukemia. 27 (8): 1707–14. doi:10.1038/leu.2013.29. PMC 3740399. PMID 23364621.
  19. ^ "European Hematology Association (EHA) 18th Congress. June 13-16, 2013". The Myeloma Beacon. 2013. Retrieved 2013-07-13.
  20. ^ "Nikoletta Lendval, MD PhD et al. Phase II Study of Infusional Carfilzomib in Patients with Relapsed or Refractory Multiple Myeloma". Presented at: 54th ASH Annual Meeting and Exposition: December 2012. Retrieved 2013-07-23.
  21. ^ "Phase II results of Study PX-171-007: A phase Ib/II study of carfilzomib (CFZ), a selective proteasome inhibitor, in patients with selected advanced metastatic solid tumors" - ASCO 2009; Abstract 3515.
  22. ^ a b c Guerrero-Garcia TA, Gandolfi S, Laubach JP, Hideshima T, Chauhan D, Mitsiades C, et al. (December 2018). "The power of proteasome inhibition in multiple myeloma". Expert Review of Proteomics. 15 (12): 1033–1052. doi:10.1080/14789450.2018.1543595. PMID 30427223. S2CID 53303519.
  23. ^ Siegel DS, Martin T, Wang M, et al. (2011-03-09). "Results of PX-171- 003-A1, an open-label, single-arm, phase 2 study of carfilzomib in patients with relapsed and refractory multiple myeloma. Presented at: 52nd ASH Annual Meeting and Exposition; December 4-7, 2010; Orlando, Florida". December 2010. OncLive.com. Retrieved 2011-09-01.
  24. ^ "Final Results of a Frontline Phase 1/2 Study of Carfilzomib Lenalidomide, and Low-Dose Dexamethasone (CRd) in Multiple Myeloma (MM)". ASH 20111; Abstract 631. Retrieved 2012-02-27.
  25. ^ Efentakis P, Kremastiotis G, Varela A, Nikolaou PE, Papanagnou ED, Davos CH, et al. (February 2019). "Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin". Blood. 133 (7): 710–723. doi:10.1182/blood-2018-06-858415. PMID 30482794.
  26. ^ "Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Versus Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma". ClinicalTrials.gov. 2011-08-04. Retrieved 2011-09-01.
  27. ^ Stenger, Matthew (January 31, 2018). "ASPIRE Trial: Final Overall Survival Results in Relapsed or Refractory Multiple Myeloma". The ASCO Post. Retrieved March 28, 2021.
  28. ^ "FDA Approves Kyprolis (Carfilzomib) For Relapsed And Refractory Multiple Myeloma". The Myeloma Beacon. Retrieved 2012-07-20.

April 12, 2024
carfilzomib, sold, under, brand, name, kyprolis, anti, cancer, medication, acting, selective, proteasome, inhibitor, chemically, tetrapeptide, epoxyketone, analog, epoxomicin, developed, onyx, pharmaceuticals, clinical, datatrade, nameskyprolisother, namespx, . Carfilzomib sold under the brand name Kyprolis is an anti cancer medication acting as a selective proteasome inhibitor Chemically it is a tetrapeptide epoxyketone and an analog of epoxomicin 4 It was developed by Onyx Pharmaceuticals CarfilzomibClinical dataTrade namesKyprolisOther namesPX 171 007AHFS Drugs comMonographMedlinePlusa612031License dataUS DailyMed CarfilzomibPregnancycategoryAU CRoutes ofadministrationIntravenousATC codeL01XG02 WHO Legal statusLegal statusAU S4 Prescription only 1 CA only 2 UK POM Prescription only US only 3 EU Rx onlyPharmacokinetic dataProtein binding97 3 MetabolismExtensive CYP plays a minor roleIdentifiersIUPAC name 2S 4 Methyl N 2S 1 2S 4 methyl 1 2R 2 methyloxiran 2 yl 1 oxopentan 2 yl amino 1 oxo 3 phenylpropan 2 yl 2 2S 2 2 morpholin 4 ylacetyl amino 4 phenylbutanoyl amino pentanamideCAS Number868540 17 4PubChem CID11556711IUPHAR BPS7420DrugBankDB08889ChemSpider9731489UNII72X6E3J5ARKEGGD08880ChEBICHEBI 65347ChEMBLChEMBL451887CompTox Dashboard EPA DTXSID4048690ECHA InfoCard100 219 957Chemical and physical dataFormulaC 40H 57N 5O 7Molar mass719 924 g mol 13D model JSmol Interactive imageSMILES O C N C H C O N C H C O N C H C O N C H C O C 1 OC1 C CC C C Cc2ccccc2 CC C C CCc3ccccc3 CN4CCOCC4InChI InChI 1S C40H57N5O7 c1 27 2 22 32 36 47 40 5 26 52 40 42 39 50 34 24 30 14 10 7 11 15 30 44 38 49 33 23 28 3 4 43 37 48 31 17 16 29 12 8 6 9 13 29 41 35 46 25 45 18 20 51 21 19 45 h6 15 27 28 31 34H 16 26H2 1 5H3 H 41 46 H 42 50 H 43 48 H 44 49 t31 32 33 34 40 m0 s1Key BLMPQMFVWMYDKT NZTKNTHTSA NThe US Food and Drug Administration FDA approved it in July 2012 5 6 Contents 1 Medical uses 2 Mechanism 3 History 4 Clinical trials amp side effects 4 1 Completed 4 2 ASPIRE trial 5 Society and culture 5 1 Economics 6 ReferencesMedical uses editThe FDA approved carfilzomib in July 2012 for use in people with multiple myeloma who have received at least two prior therapies including treatment with bortezomib and an immunomodulatory therapy such as lenalidomide and have demonstrated disease progression on or within 60 days of completion of the last therapy 5 Mechanism editCarfilzomib covalently 7 irreversibly binds to and inhibits the chymotrypsin like activity of the 20S proteasome an enzyme that degrades unwanted cellular proteins Carfilzomib displays minimal interactions with non proteasomal targets thereby improving safety profiles over bortezomib 7 Inhibition of proteasome mediated proteolysis results in a build up of polyubiquitinated proteins which may cause cell cycle arrest apoptosis and inhibition of tumor growth 4 History editCarfilzomib is derived from epoxomicin a natural product that was shown by the laboratory of Craig Crews at Yale University to inhibit the proteasome 8 The Crews laboratory subsequently invented a more specific derivative of epoxomicin named YU101 9 which was licensed to Proteolix Inc Scientists at Proteolix invented a new distinct compound that had potential use as a drug in humans known as carfilzomib Proteolix advanced carfilzomib to multiple phase I and II clinical trials including a pivotal phase 2 clinical trial designed to seek accelerated approval 10 Clinical trials for carfilzomib continue under Onyx Pharmaceuticals which acquired Proteolix in 2009 10 In January 2011 the FDA granted carfilzomib fast track status allowing Onyx to initiate a rolling submission of its new drug application for carfilzomib 11 In December 2011 the FDA granted Onyx standard review designation 12 13 for its new drug application submission based on the 003 A1 study an open label single arm phase IIb trial The trial evaluated 266 heavily pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies including bortezomib and either thalidomide or lenalidomide 14 Initial approval was based on response rate 5 Data demonstrating an overall survival benefit was demonstrated in the ENDEAVOR trial and approved by the FDA 15 Clinical trials amp side effects editCompleted edit A single arm phase II trial 003 A1 of carfilzomib in patients with relapsed and refractory multiple myeloma showed that single agent carfilzomib demonstrated a clinical benefit rate of 36 in the 266 patients evaluated and had an overall response rate of 22 9 and median duration of response of 7 8 months The FDA approval of carfilzomib was based on results of the 003 A1 trial 3 In a phase II trial 004 carfilzomib had a 53 overall response rate among patients with relapsed and or refractory multiple myeloma who had not previously received bortezomib This study also included a bortezomib treated cohort Results were reported separately 16 This study also found prolonged carfilzomib treatment was tolerable with approximately 22 of patients continuing treatment beyond one year The 004 trial was a smaller study originally designed to investigate the impact of carfilzomib treatment in relationship to bortezomib treatment in less heavily pretreated 1 3 prior regimens patients 17 A phase II trial 005 which assessed the safety pharmacokinetics pharmacodynamics and efficacy of carfilzomib in patients with multiple myeloma and varying degrees of renal impairment where nearly 50 of patients were refractory to both bortezomib and lenalidomide demonstrated that pharmacokinetics and safety were not influenced by the degree of baseline renal impairment Carfilzomib was tolerable and demonstrated efficacy 18 In another phase II trial 006 of patients with relapsed and or refractory multiple myeloma carfilzomib in combination with lenalidomide and dexamethasone demonstrated an overall response rate of 69 19 A phase II trial 007 for multiple myeloma and solid tumors showed promising results 20 21 In phase II trials of carfilzomib the most common grade 3 or higher treatment emergent adverse events were hematologic toxicity 22 with thrombocytopenia anemia lymphopenia neutropenia pneumonia fatigue and hyponatremia 23 In a frontline phase I II study the combination of carfilzomib lenalidomide and low dose dexamethasone was highly active and well tolerated permitting the use of full doses for an extended time in newly diagnosed multiple myeloma patients with limited need for dose modification Responses were rapid and improved over time reaching 100 very good partial response 24 Furthermore gastrointestinal disturbances including diarrhea and nausea are non hematologic group of side effects commonly reported with proteasome inhibitors 22 Additionally cardiovascular toxicity may be an outcome of carfilzomib treatment due to the effects on proteasomes in the myocardium 22 Thus patient evaluation and risk assessment prior to initiation of therapy with carfilzomib is crucial 25 ASPIRE trial edit A phase III confirmatory clinical trial known as the ASPIRE trial compared carfilzomib lenalidomide and dexamethasone KRd versus lenalidomide and dexamethasone Rd in patients with relapsed multiple myeloma and found improved progression free survival and overall survival Treatment discontinuation because of adverse effects occurred less frequently in the KRd arm and events included thrombocytopenia hypertension and heart failure 26 27 Society and culture editEconomics edit Carfilzomib costs approximately US 10 000 per 28 day cycle 28 References edit Prescription medicines registration of new chemical entities in Australia 2016 Therapeutic Goods Administration TGA 21 June 2022 Retrieved 10 April 2023 Health Canada New Drug Authorizations 2016 Highlights Health Canada 14 March 2017 Retrieved 7 April 2024 a b c Kyprolis carfilzomib injection powder lyophilized for solution DailyMed 26 August 2020 Retrieved 13 November 2020 a b NCI Drug Dictionary National Cancer Institute Retrieved 13 November 2020 a b c FDA Approves Kyprolis for Some Patients with Multiple Myeloma FDA 2012 07 20 Archived from the original on 2013 01 28 Retrieved 2013 07 23 Drug Approval Package Kyprolis carfilzomib for Injection NDA 202714 U S Food and Drug Administration FDA 20 August 2012 Retrieved 10 April 2023 a b Park JE Park J Jun Y Oh Y Ryoo G Jeong YS et al May 2019 Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin coated nanocrystal formulation Journal of Controlled Release 302 148 159 doi 10 1016 j jconrel 2019 04 006 PMC 6638563 PMID 30954620 Meng L Mohan R Kwok BH Elofsson M Sin N Crews CM August 1999 Epoxomicin a potent and selective proteasome inhibitor exhibits in vivo antiinflammatory activity Proceedings of the National Academy of Sciences of the United States of America 96 18 10403 8 Bibcode 1999PNAS 9610403M doi 10 1073 pnas 96 18 10403 PMC 17900 PMID 10468620 Myung J Kim KB Lindsten K Dantuma NP Crews CM February 2001 Lack of proteasome active site allostery as revealed by subunit specific inhibitors Molecular Cell 7 2 411 20 doi 10 1016 S1097 2765 01 00188 5 PMID 11239469 a b Carfilzomib From Discovery To Drug Chemical amp Engineering News 2012 08 27 Retrieved 2013 07 30 Onyx multiple myeloma drug wins FDA fast track status San Francisco Business Times 2011 01 31 Retrieved 2011 09 01 Beacon Breaking News Carfilzomib to Get Standard Not Priority FDA Review The Myeloma Beacon Retrieved 2012 02 27 Fast Track Accelerated Approval and Priority Review Accelerating Availability of New Drugs for Patients with Serious Diseases FDA Archived from the original on 2012 02 17 Retrieved 2012 02 27 PX 171 003 A1 an open label single arm phase Ph II study of carfilzomib CFZ in patients pts with relapsed and refractory multiple myeloma R R MM Long term follow up and subgroup analysis ASCO 2011 Abstract 8027 2011 Archived from the original on 2012 03 23 Retrieved 2011 09 01 Broderick JM 18 January 2018 FDA Approves Carfilzomib Label Update in Myeloma OncLive Retrieved 10 April 2023 Vij R Siegel DS Jagannath S Jakubowiak AJ Stewart AK McDonagh K et al September 2012 An open label single arm phase 2 study of single agent carfilzomib in patients with relapsed and or refractory multiple myeloma who have been previously treated with bortezomib British Journal of Haematology 158 6 739 48 doi 10 1111 j 1365 2141 2012 09232 x PMC 5818209 PMID 22845873 Vij R Wang M Kaufman JL Lonial S Jakubowiak AJ Stewart AK et al June 2012 An open label single arm phase 2 PX 171 004 study of single agent carfilzomib in bortezomib naive patients with relapsed and or refractory multiple myeloma Blood 119 24 5661 70 doi 10 1182 blood 2012 03 414359 PMC 4123327 PMID 22555973 Badros AZ Vij R Martin T Zonder JA Kunkel L Wang Z et al August 2013 Carfilzomib in multiple myeloma patients with renal impairment pharmacokinetics and safety Leukemia 27 8 1707 14 doi 10 1038 leu 2013 29 PMC 3740399 PMID 23364621 European Hematology Association EHA 18th Congress June 13 16 2013 The Myeloma Beacon 2013 Retrieved 2013 07 13 Nikoletta Lendval MD PhD et al Phase II Study of Infusional Carfilzomib in Patients with Relapsed or Refractory Multiple Myeloma Presented at 54th ASH Annual Meeting and Exposition December 2012 Retrieved 2013 07 23 Phase II results of Study PX 171 007 A phase Ib II study of carfilzomib CFZ a selective proteasome inhibitor in patients with selected advanced metastatic solid tumors ASCO 2009 Abstract 3515 a b c Guerrero Garcia TA Gandolfi S Laubach JP Hideshima T Chauhan D Mitsiades C et al December 2018 The power of proteasome inhibition in multiple myeloma Expert Review of Proteomics 15 12 1033 1052 doi 10 1080 14789450 2018 1543595 PMID 30427223 S2CID 53303519 Siegel DS Martin T Wang M et al 2011 03 09 Results of PX 171 003 A1 an open label single arm phase 2 study of carfilzomib in patients with relapsed and refractory multiple myeloma Presented at 52nd ASH Annual Meeting and Exposition December 4 7 2010 Orlando Florida December 2010 OncLive com Retrieved 2011 09 01 Final Results of a Frontline Phase 1 2 Study of Carfilzomib Lenalidomide and Low Dose Dexamethasone CRd in Multiple Myeloma MM ASH 20111 Abstract 631 Retrieved 2012 02 27 Efentakis P Kremastiotis G Varela A Nikolaou PE Papanagnou ED Davos CH et al February 2019 Molecular mechanisms of carfilzomib induced cardiotoxicity in mice and the emerging cardioprotective role of metformin Blood 133 7 710 723 doi 10 1182 blood 2018 06 858415 PMID 30482794 Phase 3 Study Comparing Carfilzomib Lenalidomide and Dexamethasone CRd Versus Lenalidomide and Dexamethasone Rd in Subjects With Relapsed Multiple Myeloma ClinicalTrials gov 2011 08 04 Retrieved 2011 09 01 Stenger Matthew January 31 2018 ASPIRE Trial Final Overall Survival Results in Relapsed or Refractory Multiple Myeloma The ASCO Post Retrieved March 28 2021 FDA Approves Kyprolis Carfilzomib For Relapsed And Refractory Multiple Myeloma The Myeloma Beacon Retrieved 2012 07 20 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Carfilzomib amp oldid 1217672649, wikipedia, wiki, book, books, library,

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