Hospital Practice
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Elevated Creatine Kinase and Malignancy Charis Eng, Alan E. Skolnick & Steven E. Come To cite this article: Charis Eng, Alan E. Skolnick & Steven E. Come (1990) Elevated Creatine Kinase and Malignancy, Hospital Practice, 25:12, 123-130, DOI: 10.1080/21548331.1990.11704052 To link to this article: http://dx.doi.org/10.1080/21548331.1990.11704052
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [La Trobe University]
Date: 19 June 2016, At: 22:56
Brief Review
Elevated Creatine Kinase and Malignancy CHARIS ENG, ALAN E. SKOLNICK.
and
STEVEN E. COME
Downloaded by [La Trobe University] at 22:56 19 June 2016
Haroard University
Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumors with poor prognosis.
For the past 30 years, measurement of serum creatine kinase has been used to reflect diseases of myocardium, skeletal muscle, and the central nervous system. Classically, an increase in the myocardial-specific enzyme, CK-MB, is the hallmark of acute myocardial infarction; CK-BB and CK-MM isoenzymes are elevated in acute cerebral and skeletal muscle injuries, respectively. Elevations of CKMB, CK-BB, and variant CKs have been reported in a variety of malignancies in the absence of obvious cardiac, muscular, or brain injury.
Electrophoretic CK Variants Creatine kinase is a dimer composed of combinations of the M subunit and the B subunit. The main methods of isoenzyme determination are electrophoresis, ion exchange chromatography, immunoprecipitation, and radioimmunoassay. Of these, electrophoresis is relatively simple and quick. It is less sensitive, however, than chromatography. The latter is labor-
intensive, but when good columns and elution techniques are used, it often results in more precise separation of CK variants. Immunoinhibition is less sensitive and specific than either electrophoresis or chromatography. Finally, radioimmunoassay is 10 times more sensitive than chromatography for separation of CK isoenzymes. Electrophoresis is more commonly used in the clinical laboratory. With this technique, CK-BB migrates to the anode, CK-MM to the cathode, and CK-MB between the BB and MM bands. Macro-CK is electrophoretically located between the MB and MM bands and is composed of CK-BB or CK-MM complexed to another serum protein, thought to be immunoglobulin or ,8-lipoprotein. Mitochondrial CK (CK-MIT) is another variant that migrates toward the CKMM, but it is unclear whether it is distinct from Macro-CK
Malignancy-Associated Elevation of CK Ten years ago, Roy L. Alexander reported the case of a 69-
year-old man with stageD prostate cancer who was admitted with an acute myocardial infarction diagnosed by electrocardiography and elevation of CK-MB. However, the elevation persisted into the fourth and fifth day after infarction. In addition, the patient demonstrated CK-BB elevations without clinical evidence of cerebral injury. Alexander proposed that the persistent elevations of MB and BB fractions represented neoplastic secretions. Four years later, Barry Stein and Fram Dalal reported a similar case of a 79-year-old man with stage D prostate cancer who presented with chest pain and elevations of both CK-MB and CK-BB, detected by immunoinhibition. At autopsy, however, the patient had no evidence of myocardial infarction. That suggested that the prostate cancer had synthesized both CKs. On reexamination by electrophoresis, it was found that only the CK-BB was markedly elevated; the MB fraction was within normal limits. It was noted that the immunoinhibition assay may result in a falsely elevated MB fraction. Nevertheless, the patient's increased CK-BB was attributed to paraneoplastic synthesis. In response to these initial reports, investigators undertook to determine whether CK was elaborated by other tumors. (continues)
Drs. Eng and Skolnick are Clinical Fellows and Dr. Come is Associate Professor of Medicine, Harvard MedIcal School. At Beth Israel Hospital, Boston, Dr. Eng is a Senior Resident and Dr. Skolnick is a Junior Resident, Department of Medicine, and Dr. Come is the Director of the Hematology-Oncology Ambulatory Unit, Division of Hematology and Medical Oncology. Hospital Practice December 15. 1990
123
Seldane®
(llrfenadine)60 ma 1'lbllts IlifF IUMIIAR\' CAUTION: -rallawprallibilsdisplnsin1!wi1houtprescriplian.
DliCRIPTIOII
Seldane (terfenldine) is Mil&ble as lltMts tor cnlldministrltion. Each
CREATINE KINASE
(continued)
tltMt contains 60 mg tlfflnadine. 1'1111111111SG contain, as inKti¥1 in:9rtdients: com stan:h, gelltin, lactose, magnesium stume, and sodium bicarbonate. 11--AIIDUUII£ Seldane is Indicated lor thl nllill at symptoms ISSOdlted with seasonal dergic rf'linitis such as sneezing, rhinorrhll. pruritus, and lacrimation.
CDIITRAINDICATIDIII
Stldane is
contraindiclted in patients with
terfanadine or any of tts ingredients.
a known hypersensitiVIty to
PRECAUTIDIII Genef.ll: Terfenadine und11goes IX1tnsivl melabolism in tbe li~. PatientS
with tmpairtd hepatic function (alcoholic C!rrhosls, ~epatitts). or on klloconazole or troStandomycin ttlerapy, 01" hiVIng condiltons leadtng toOT
~~~~~~~=:~~~u~~~r:~~~~~o,:J~:e~:nc:,n;~
The effect ot tlffenadine in patients who are receiving agents whiCh alter the OT interval is not known. These 11111nts hM Mso occurred in patients on macrolide antibiotics, including erythrol1\ttin, but causality is unclear. 1llt events may be re<td to ahered metabolism of the drug, to electrolyte lrnbatance, orbottl. lnformltion lortMlitnts: Patients takinq Seldane should recliwl the follow-
=rm::o~i~~~o~~~ti:~=:.:~':O~r=~~:u:
Downloaded by [La Trobe University] at 22:56 19 June 2016
t
Llctltions:;tore starting Seldanetherapy, since the drug should used in pregnancy or lactation only it the potential benefit justifies the potential risk 10 fetus or batJIJ. Patients should be Instructed to take Saldana only_as needed and not to exceed thl prescribed dose. Patients shou~ also be 1nstructed 10 store lhis medication in a tighlty closed container ma cool. dry place, IWIY from hut or direct sunlight, and WRf tram children. Drug lnttrletions: Preliminary IVid~nceexlsts that concurrent kll~cona DM or mKrolide administration s19nificantly alters the metabolism or ttrflnadlne. COncurrent use of Seldane with ketoconazoll ortrollandomycin is not recommended. Concurrent use or other macrolidls should be approached with caution. c.c;nogenesis. mutagenesis, lmplirment olltttility: Oral dose~ of terltnadine, corresponding to 63 times the recommended human d~1ty dose. In mice for 18 months or in rats for 24 months, rMaled no ev•dence of tumorigenicity. Microbial and micronudeUs tes1 assays with terfenadine hM rwuled no MHnce or mutagenesis. Reproduction and ftrtillty studies in rats showed no effects on male or female at oral doses of up to 21 times the ~uman daily dose. N. ~ times
fertility
=~~tid~=-huu::=:~~:=sred~~:=r=
Implantation losses Wlnl observed, which were judged to be secondary to maternal toxicity. Prtt/tiMPCY Cltegofy C: There was no evidence of animal teratogenicity. AeDraduction studies hM been performed in rats at doses 63times and 125 times the human d~ose and have ~aled decreased pup weight
=
rn~==~r~: 1are n~:u:::a=n:r:e"£~~~~r:~~~f:s~
=':tnlu=:'~:'::nt ~S:t:~Lt~nancy only rr ttHI
NonterltOglnic effects: Se1dane is not recommended tor nufS:ing women.
::!'3~::a~2~~~~~~=gd~i~=h~=~~rp;;nga~ ~=~=:~:P::.::::~u~:S~:=
during lactation. Ptdiltricuse: Safety and effectiveness of SHIII'II in children below the age of 12 years hM not been ISiabUshed.
AIMIIERucnDIII
Experiencetromclinicalstudies.indudingbottlcontrolledand~
studies involving more than 2,400 patients who recewed Seidane. prOVIdes Information on adverse experience incidenc_e for periods of a_ lew d_ays up 10 six months. The usual dose in these studies was 60 mg twice dilly, but in a small number ol patients. the dose was as low as 20 mg twice a day, or as high as 600 mg daily. In controlled clinical studies using the recomm_endld dose of 60 mg b.i.d.,
:J~0:e~~4nld;t':t:",:~~n~:~:rs:~=::V,":)
--... .......-
ADV£111£ MNTI REPDIITED IN CUNICAL TRIAU
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ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Elevated Creatine Kinase and Malignancy Charis Eng, Alan E. Skolnick & Steven E. Come To cite this article: Charis Eng, Alan E. Skolnick & Steven E. Come (1990) Elevated Creatine Kinase and Malignancy, Hospital Practice, 25:12, 123-130, DOI: 10.1080/21548331.1990.11704052 To link to this article: http://dx.doi.org/10.1080/21548331.1990.11704052
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [La Trobe University]
Date: 19 June 2016, At: 22:56
Brief Review
Elevated Creatine Kinase and Malignancy CHARIS ENG, ALAN E. SKOLNICK.
and
STEVEN E. COME
Downloaded by [La Trobe University] at 22:56 19 June 2016
Haroard University
Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumors with poor prognosis.
For the past 30 years, measurement of serum creatine kinase has been used to reflect diseases of myocardium, skeletal muscle, and the central nervous system. Classically, an increase in the myocardial-specific enzyme, CK-MB, is the hallmark of acute myocardial infarction; CK-BB and CK-MM isoenzymes are elevated in acute cerebral and skeletal muscle injuries, respectively. Elevations of CKMB, CK-BB, and variant CKs have been reported in a variety of malignancies in the absence of obvious cardiac, muscular, or brain injury.
Electrophoretic CK Variants Creatine kinase is a dimer composed of combinations of the M subunit and the B subunit. The main methods of isoenzyme determination are electrophoresis, ion exchange chromatography, immunoprecipitation, and radioimmunoassay. Of these, electrophoresis is relatively simple and quick. It is less sensitive, however, than chromatography. The latter is labor-
intensive, but when good columns and elution techniques are used, it often results in more precise separation of CK variants. Immunoinhibition is less sensitive and specific than either electrophoresis or chromatography. Finally, radioimmunoassay is 10 times more sensitive than chromatography for separation of CK isoenzymes. Electrophoresis is more commonly used in the clinical laboratory. With this technique, CK-BB migrates to the anode, CK-MM to the cathode, and CK-MB between the BB and MM bands. Macro-CK is electrophoretically located between the MB and MM bands and is composed of CK-BB or CK-MM complexed to another serum protein, thought to be immunoglobulin or ,8-lipoprotein. Mitochondrial CK (CK-MIT) is another variant that migrates toward the CKMM, but it is unclear whether it is distinct from Macro-CK
Malignancy-Associated Elevation of CK Ten years ago, Roy L. Alexander reported the case of a 69-
year-old man with stageD prostate cancer who was admitted with an acute myocardial infarction diagnosed by electrocardiography and elevation of CK-MB. However, the elevation persisted into the fourth and fifth day after infarction. In addition, the patient demonstrated CK-BB elevations without clinical evidence of cerebral injury. Alexander proposed that the persistent elevations of MB and BB fractions represented neoplastic secretions. Four years later, Barry Stein and Fram Dalal reported a similar case of a 79-year-old man with stage D prostate cancer who presented with chest pain and elevations of both CK-MB and CK-BB, detected by immunoinhibition. At autopsy, however, the patient had no evidence of myocardial infarction. That suggested that the prostate cancer had synthesized both CKs. On reexamination by electrophoresis, it was found that only the CK-BB was markedly elevated; the MB fraction was within normal limits. It was noted that the immunoinhibition assay may result in a falsely elevated MB fraction. Nevertheless, the patient's increased CK-BB was attributed to paraneoplastic synthesis. In response to these initial reports, investigators undertook to determine whether CK was elaborated by other tumors. (continues)
Drs. Eng and Skolnick are Clinical Fellows and Dr. Come is Associate Professor of Medicine, Harvard MedIcal School. At Beth Israel Hospital, Boston, Dr. Eng is a Senior Resident and Dr. Skolnick is a Junior Resident, Department of Medicine, and Dr. Come is the Director of the Hematology-Oncology Ambulatory Unit, Division of Hematology and Medical Oncology. Hospital Practice December 15. 1990
123
Seldane®
(llrfenadine)60 ma 1'lbllts IlifF IUMIIAR\' CAUTION: -rallawprallibilsdisplnsin1!wi1houtprescriplian.
DliCRIPTIOII
Seldane (terfenldine) is Mil&ble as lltMts tor cnlldministrltion. Each
CREATINE KINASE
(continued)
tltMt contains 60 mg tlfflnadine. 1'1111111111SG contain, as inKti¥1 in:9rtdients: com stan:h, gelltin, lactose, magnesium stume, and sodium bicarbonate. 11--AIIDUUII£ Seldane is Indicated lor thl nllill at symptoms ISSOdlted with seasonal dergic rf'linitis such as sneezing, rhinorrhll. pruritus, and lacrimation.
CDIITRAINDICATIDIII
Stldane is
contraindiclted in patients with
terfanadine or any of tts ingredients.
a known hypersensitiVIty to
PRECAUTIDIII Genef.ll: Terfenadine und11goes IX1tnsivl melabolism in tbe li~. PatientS
with tmpairtd hepatic function (alcoholic C!rrhosls, ~epatitts). or on klloconazole or troStandomycin ttlerapy, 01" hiVIng condiltons leadtng toOT
~~~~~~~=:~~~u~~~r:~~~~~o,:J~:e~:nc:,n;~
The effect ot tlffenadine in patients who are receiving agents whiCh alter the OT interval is not known. These 11111nts hM Mso occurred in patients on macrolide antibiotics, including erythrol1\ttin, but causality is unclear. 1llt events may be re<td to ahered metabolism of the drug, to electrolyte lrnbatance, orbottl. lnformltion lortMlitnts: Patients takinq Seldane should recliwl the follow-
=rm::o~i~~~o~~~ti:~=:.:~':O~r=~~:u:
Downloaded by [La Trobe University] at 22:56 19 June 2016
t
Llctltions:;tore starting Seldanetherapy, since the drug should used in pregnancy or lactation only it the potential benefit justifies the potential risk 10 fetus or batJIJ. Patients should be Instructed to take Saldana only_as needed and not to exceed thl prescribed dose. Patients shou~ also be 1nstructed 10 store lhis medication in a tighlty closed container ma cool. dry place, IWIY from hut or direct sunlight, and WRf tram children. Drug lnttrletions: Preliminary IVid~nceexlsts that concurrent kll~cona DM or mKrolide administration s19nificantly alters the metabolism or ttrflnadlne. COncurrent use of Seldane with ketoconazoll ortrollandomycin is not recommended. Concurrent use or other macrolidls should be approached with caution. c.c;nogenesis. mutagenesis, lmplirment olltttility: Oral dose~ of terltnadine, corresponding to 63 times the recommended human d~1ty dose. In mice for 18 months or in rats for 24 months, rMaled no ev•dence of tumorigenicity. Microbial and micronudeUs tes1 assays with terfenadine hM rwuled no MHnce or mutagenesis. Reproduction and ftrtillty studies in rats showed no effects on male or female at oral doses of up to 21 times the ~uman daily dose. N. ~ times
fertility
=~~tid~=-huu::=:~~:=sred~~:=r=
Implantation losses Wlnl observed, which were judged to be secondary to maternal toxicity. Prtt/tiMPCY Cltegofy C: There was no evidence of animal teratogenicity. AeDraduction studies hM been performed in rats at doses 63times and 125 times the human d~ose and have ~aled decreased pup weight
=
rn~==~r~: 1are n~:u:::a=n:r:e"£~~~~r:~~~f:s~
=':tnlu=:'~:'::nt ~S:t:~Lt~nancy only rr ttHI
NonterltOglnic effects: Se1dane is not recommended tor nufS:ing women.
::!'3~::a~2~~~~~~=gd~i~=h~=~~rp;;nga~ ~=~=:~:P::.::::~u~:S~:=
during lactation. Ptdiltricuse: Safety and effectiveness of SHIII'II in children below the age of 12 years hM not been ISiabUshed.
AIMIIERucnDIII
Experiencetromclinicalstudies.indudingbottlcontrolledand~
studies involving more than 2,400 patients who recewed Seidane. prOVIdes Information on adverse experience incidenc_e for periods of a_ lew d_ays up 10 six months. The usual dose in these studies was 60 mg twice dilly, but in a small number ol patients. the dose was as low as 20 mg twice a day, or as high as 600 mg daily. In controlled clinical studies using the recomm_endld dose of 60 mg b.i.d.,
:J~0:e~~4nld;t':t:",:~~n~:~:rs:~=::V,":)
--... .......-
ADV£111£ MNTI REPDIITED IN CUNICAL TRIAU
---
AI/CIItlal._.. -~--
c.tnlloii1Niol'
hm
Conii>-Sjstlm
9.0 63 2.9 1.• 0.9 0.9 0.1
11 71 0.9 1.1 0.2 0.6 D.D
D~qe•--1
u
3.0
27
Illy-~
2.3 0.9 0.5 0.0
1.1 0.2 0.3 0.1
3.5 0.5 0.5 0.2
1.0
17
,.
--Fl1igot
Appo1ib-
111 31 5.1 1.0 06 02 0.0
~~--
I=ZC bMJI
15 15.1 •.5 1.5 17 0.6 0.5
82 112 3.0 1.2 1.0 05 D.D
-oSjS1tm
-Di1111ss -.Voni1ilg.
E,.!Jt.llost.llld~
Cautl!
Sen~
sa.~!ruptionfinclldill""' llld1111CniO
