Pharm 54 Chemo
Transcript of Pharm 54 Chemo
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Pharm 54: Cancer Chemotherapy
ug Use Dose Mech Contraindications
Toxicity/side efects Interactionw/otherdrugs
KYLATINAGENTS
!orms D"#cross $in%s inhi&ition o!D"# synth and!unc
&inds "' on (guanine toanother
resistance inca&i$ity to repairD"#) dec drugtransport) incg$utathione*con+ugation o!drug,
#cute- "/.De$ayed moddepression o!periphera$ &$oodcount) mye$osupp)a$opecia
(chloroyl)amin
ch$orethane
0" 0
sterility-vesicant(eye/mucosal
ain) ! irritationan"
e#travasationsu$!an -$%L
pre 1Mtransp$ant
assoc ! s&ini'mentationulm *rosis
a"renalinsu+ciency SE,E E
myelosu ression
c$ophospmide
&reast)o2arian ca
" 0C00so!t tissue
sarcoma
neuro&$astomawi$ms tumor
rha&domyosar
-re.uires012 3or
activation tophosphoramidemustard andacro$ein
hemorrha'iccystitis *accum o!
acro$ein pre2entedw ade3uatehydration ormercapatoethanoesu$!onate M "#,
cardiac dys!unc)pu$m tox) I#D
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coma6#
$pha$an mu$tip$emye$oma
&r) o2arian C#
otepa 1r) o2arian casuper7cia$&$adder C#
$oram&uc C00) " 0
rosoure car&amoy$ationo! $ysineresidues o!P68 isocyanate!ormation
re3uire&iotrans!ormation in 2i2o
$ipid so$u&$ecrosses 11&arrier
-n/v-myelosuinterstitial lun'"4 interstitialne hritis -$NS T56-convulsionsata#ia "i44iness
rmustine 1rain C#0
" 0mustineepto9oci insu$in
secreting is$etC# o! pancreas
natura$$yoccuring
min mye$osupp
retamine o2arian C# "/.mye$osupp)
periphera$neuropathy) u $i%esyndrome
nclassic
&ylatin'nts
methylates7NA an"inhi*itssynth/3unc
dec 6"#) prosytn) incinterphase) D"#strand &rea%s
car&a9in 0" 01rain tumor
inhi&its M#8inhi&itors
!orms h;o;generating !ree
alcohol-"isul3ram-li&e r#n
-leu&emo'enic-8 n" A%L-acute- $NS"e ression
don
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radica$ strandscission
-"elaye"-myelosu 9Ss&in
sympaths) tricyc$antidepressas) anti D
antihistaminC"depressa
car&a9in 0Me$anomaso!t tissue
sarcoma
"euro&$astoma=idstumors-so!ttissue
acti2ated &y$i2er tomonomethy$deri2ati2e dia9omethane)toxic methy$car&onium ion
#1.D regimenused !or D)$ess $i%e$y tocausesteri$ity/; nd C#than M8PP
-acute-N/,-"elaye"-myelosu cnsto# !neuro athyata#ia lethar'ycon3usion
phototox) u $i%esyndrome
2esicant &$isters
ndamusti :; st line colonca ! 1
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an" nuclearro
ta#anes
p$atin non/sma$$ ce$$$ung C#
&reast)
&$adder)head/nec%)'astroeso ha'eal 'ermcelltesticular(non-seminoma , )o2arian ca
a$%y$atingagent
nephro and ototox"8 1MUPP6 I8"
inctoxicitiesaminog$
ides-ami3osti(3reera"icalscaven3cl "iures"ecne hroto
r&op$atin non/sma$$ ce$$$ung C#
&reast)&$adder)head/nec%)o2arian
; nd $inep$atinum
-'reatermyelosu-acute? N/,-less ne hronto# rarely
eri heralneuro athymore li&ey renalto# he atic"ys3unc
hearing $oss)tinnitus $ess
$ess rena$) @I toxa$ip$atin tumors
resistant tocis latincar*o latinw/ uoropyrimidine *5 AU,and $euco2orin)&endamustine
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uorouraci$AU,
anal *reast )gastroesophagea$) head/nec%)hepatoce$$u$ar
stomach
pancreas-*asal cellcarcinoma(to ica $,
t(/;( (5min
thymi"inesynthase-incor ates
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-inhi*itsthymi"inesynthase-inhi*its "enovo urine
nucleoti"esynthesis!o$ic acid
ana$ogthotrexat Breast
head/nec%)&$adder
osteogenicsarcoma
primary C"$ymphoma
" 0
chroiocarcinoma- A
soriasisEcto icre'nancy
I.)intratheca$)ora$
!ormation o!po$yg$utamate!or cytotoxicefects
resistance decaccum o! drug)dec sensiti2ity)dec !ormationo!po$yg$utamate)a$ter D A6)transporters/carrier P68s
ad+ust dose!or rena$dys!unc*rena$$yc$eared,
mucosititisdiarrheamye$osupp
neutropenia)throm&ocytopenia>>need ade3uatehydration
macro2esicu$ar!atty change in$i2er
anti"oteleucovor
care!u$aspirin/"Ds) PC"cepha$oins inhirena$excretion
metrexed mesothe$iomanon sma$$ ce$$
$ung C#; nd $ine
mesothe$ioma/non sma$$ ce$$$ung C#
w cisp$atin ( st
$inemesothe$ioma)non sma$$ ce$$$ung
most acti2ityinhi&iting Tsynthase
mye$osupps%in rashmucositisdiarrhea) !atiguehand !oot
syndrome *txdexamethasone,
w !o$icacid/&(;reducetoxicities
$atrexate re$apsed)re!ractory Tce$$ $ymphoma
mye$osupp) rash)mucositis) diarrhea)!atigue
w !o$icacid/&(;reducetoxicities
o#ycytiealo'stara&ine &$ood
ma$ignancies8"0 no
Inhi&its D"#Chaine$ongation) D"#
"#U #.8MITI"@
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acti2ity 2sso$id tumors
#M0#00CM0 I" 10# T
C6I I" 0
synthesis andrepair *D"#po$ymeraseinhi&itors,
Inhi&its
6i&onuc$eotidereductase withreduced!ormation o!d"TPs
Incorporationo! @ MCIT#1I"triphosphateinto D"#resu$ting ininhi&ition o!
D"# synthesisand !xD6U@ I#CTI.#T D 1=I"# T8#6# CTP- #"I" I1IT86 8AD"#P80 M 6#*# synthesis)1 repair,-M8 T
P CIAICI" I1IT86 A86
P # 8AC 00 C C0
%YEL5S= ESSI5N-
ancyto enia!/me'alo*lasticanemia
C 6 1 00#6#T#EI# *neurotox,mucositis
mcita&in Pancreatic)&$adder)&reast) nonsma$$ ce$$ $ung)o2arian cancer
" 0o!t tissue
sarcoma
Inhi&its D"#Chaine$ongation) D"#synthesis andrepair *D"#po$ymeraseinhi&itors,
Inhi&its6i&onuc$eotidereductase withreduced!ormation o!d"TPs
Incorporationo! cytara&ine
"#U #.8MITI"@DI#66 #
M 08 UPP6 I8" neutropenia
PU0M8"#6 T8EICIT
u $i%e syndromerare hemo$ytic
uremic synd)throm&ocytopenicpurpura) rena$microangiopathy
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triphosphateinto D"# resu$tin inhi&ition o!D"# synthesisand !x
rineta'onist
opurines#00#M0CM0
I1D
I" I1IT D"8. PU6I""UC0 8TID
"T*I"C86P86#TI8" 8A
T6IP 8 P #TI"T8 D"# G6"#,-ANALOG OFHYPOXANTINE
D6U@ #6 ACTIVATED BYHYPOXANTHANINE-GUANINPHOSPHORIBOSLYTRANSFERASE TO TOXICMETABOLITES(HGPRTASE)
6 I T#"C.I#D C6 # D
@P6T##CTI.IT 86I"C6 # DP68DUCTI8"8A #0=#0I"P 8 P #T#
dec guanosinenuc$eotidesinhi&itsg$ycoprosynthesis )thiopurinesinto D"#/6"#
%YEL5S= ESSI5N
IMMU"8 UP66 I8"9E AT5T56I$ITY
*C 80 T# I ) H#U"DIC )" C68 I ,
18" M#668UPP6 I8"
-GI to#
USEDTXCYCLOSPHAMINDUCCYSTIHEMMGITIS
-INTERAN WITH
ALLOPUOLREQUIRDOSEREDUC
synergiwcytara&i!or adu$acute$eu%em
chi$dhood I" I1IT D M T#180I
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rcaptopue *F MP,
acute $eu%emia#M0CM0
I1D
"8. PU6I""UC0 8TID
"T*I"C86P86#TI8" 8A
T6IP 8 P #TI"T8 D"# G6"#,-ANALOG OFHYPOXANTINE
D6U@ #6 ACTIVATED BYHYPOXANTHANINE-GUANINPHOSPHORIBOSLYTRANSFERAS
E TO TOXICMETABOLITES(HGPRTASE)
6 I T#"C.I#D C6 # D
@P6T##CTI.IT 86I"C6 # DP68DUCTI8"8A #0=#0I"P 8 P #T#
%YEL5S= ESSI5N
IMMU"8 UP66 I8"
9E AT5T56I$ITY *C 80 T# I ) H#U"DIC )" C68 I ,
18" M#668UPP6 I8"
-GI T56
M 8A F1E#"T"8EID#
I" I1IT1#008PU80 #"DA 1UE
TUSED
TXCYCLOSPHAMINDUCCYSTIHEMMGITISINTERON WI
ALLOPOLREQUDOSEREDUN
udara&ine $ow grade " 0C00 dephosphory$at
ed) ICphosphory$atedtotriphosphate incorporatedinto D"# inhi&its synthand !unc)inhi&its D"#po$y a*synthesis, andpo$y & *repair,
induces ce$$apoptosis
mye$osupp-inhi*itorye@ects on $70$7 - inc ris& 3or'un'i her es
Ciroveci ('ivesul3-tm )
adri&ine hairy ce$$ triphosphate mye$osupp
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$eu%emiaC00$ow grade " 0
!orm in 2i2oincorporatedinto D"#inhi&its D"#po$ym *a and &,
purinenuc$eosideana$og
dec CD4) CDJ Tce$$s
AT= AL57=$T$9E%5
=GSca&aloi"s
inhi&itsmitosis Inhi&itthe !ormation o! the mitoticspind$e &ypre2enting theassem&$y o!tu&u$in dimersin MT
#ct primari$y atthe % hase
-6 I T#"C.I#I"C6 # D
AA0UE .I#M M16#"D6U@
T6#" P86T 6-@I. "P#6#T 6"#00-1I0I#66C0 #6 D
modi!ydosing in$i2erdys!unc
P45meta&o$
&$astine 0" 0@ 6M C 00
C#"C 616 # T
C#"C 6KA 5SI
SA $5%ATESTICULAR
CANCER
#CUT - ") .D 0# D- . 6
M 08 UP6 I8") MUC8 ITI )#08P CI#) I#D ).# CU0#6 . "T
cristine #00 #CUT - "8"
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0-NHL6 #1D8M 8#6C8M#" U6810# T8
M#I0M TUM86w prednisone
remissioninduction in#00 in %ids
mu$tip$emye$oma
ewingsarcoma
=ID TUM86
D 0# D-NEUROTOXICITYWITH PERIPHERALNEUROPATHY(AREFELXIA +
FOOT DROP WPINS ANDNEEDLESSENSATION)
A ALYTI$ ILE=SM 08 UP6 I8"
mi$d) #08P CI#)I#D
ore$&ine "8" M#00C 00 0U"@C#"C 6
16 # TC#"C 6
8.#6I#"C#"C 6
#CUT - ") .D 0# D-%YEL5S= ESSI5N/ neutro eniaC8" TIP#TI8")
I#Dinc $i2er !unc tests
#anes B EAST$AN$E
"8" M#00C 00 #"D
M#00 C 000U"@ C#"C 6-5,A IAN )@# T68 8P#@ #0)P68 T#T )10#DD 6)
#D/" C=C#"C 6
- INTERACTWITHMICROTUBULES(but un !"#$!n%& ' !%
*#$#nt+!,&,,# b . /0tubu #,)1 ITSTABILI2ESTUBULIN ANDCELLS REMAINFRO2EN INMETAPHASE *nomicrotu&u$eassoc pro)@TP, inhi&itsmitosis ce$$death
-myelosualo eciahy ersensitivity
c$itaxe$ =aposisarcoma*#$&raxanea$&umin &ound!ormu$a,
I. P45meta&o$ism
reducedose w $i2erpro&s
#CUT - ") .)P8T " I8")
#66 T MI# )P 6 " ITI.IT
D 0# D-
dexametone)diphenhymine) h;&$oc%e
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metastatic&reast cancer$essmye$osupp) re2neurortox
M 08 UP6 I8") P 6IP 6#0
" 86" U68P#T
reduce
cetaxe$ ;nd
$inead2anced&reast cancer
D 0# D-" U68T8EICIT#"D 18"M#668D P6 I8"
&a9itaxe$ mu$tidrugresistanttumors
w/prednisone; nd $inehormonere!ractorymetastaticprostatecancerpre2ious$ytreated wdocetaxe$regimen
poor su&strate!or mu$tidrugresistant Pg$ycoproteineKux pump
mye$osuppneurotox
6
&epi$one metastatic&reast cancerw/
uoropyrimidine)capecita&ine)mono
direct$y &indsto 1 tu&u$insu&units onmicrotu&u$es)inhi&itsmicrotu&u$edynamics
acti2e in Mphase
mye$osupp6
periphera$ sensoryneuropathy
i o"o hoto#ins
"8" M#00C 00 #"DS%ALL $ELL$A $IN5%A5< L=NG
0" 0@# T6IC
C#"C 6TESTICULAR
CANCERhigh dose
transp$antsetting !or
inhi*itsto oisomerase 8 7NA*rea&s/"e'ra"ation
-M8 T #CTI.I" 0#T #"D
#60 @;P #
-6 "#00C0 #6 D
#CUT - ") .)P8T " I8"
D 0# D- AL5 E$IA%YEL5S= ESSI5N GI to#
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&reast ca)$ymphomas
poside 8ra$)I.
m tothes inhi*itsto oisomerase ; *cuts andre$egates sing$eD"# strands,inhi&itioncauses D"#damage- reventsun!in"in'an"re lication
#CUT - D) ") .D 0# D-%YEL5S= ESS=5N N 7 ) .
otecan S%ALL $ELLL=NG$AN$E (8 n" )-a"v5,A IAN$AN$E
; nd $ine a!terp$atinumchemo used
e$iminatedrena$$y
notecan $5L5 E$TAL$AN$E@# T68 8P#@ #0C#"C 6
"8" M#00C 00 #"D
M#00 C 00C#6CI"8M#( st $ine co$oncancer w 5 AU)$euco2orin
P68D6U@C8". 6T D I"0I. 6 T8#CTI.M T#180IT
" BJ- 0IMI"#T DI" 1I0 /A Cmore potent
inhi&itor
mye$osuppdiarrhea
NTIT=%5
NTIBI5TI
thracycls
I. Inhi&it TopoisomeraseII and 'enerate56YGEN 3reera"icals that
A$=TE? E7= INE (N5T9E%AT= IA)7ELAYE7?
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*loc& thesynthesis o3
NA an" 7NAan" cause "s-7NA stran"
scissionMem&ranedisruption a$ter
uidity) iontransport
Interca$ateinto D"#-C0 #6 D I"1I0 G U6I"DEXRAZOXANE=INHIBITOROF FE-MEDIATEDFREE RADICALGENERATION
AND MAYPROTECT
AGAINST DOSEDEPENDENTCARDIOTOXICITY
$A 7I5T56I$ITY($9< D$A 7I5%Y5 AT9
Y ,) #08P CI#)M 08 UP6 I8"
neutron/throm&openias) T8M#TITI$A 7I5 T56Acute-arrhythmiascon"uction
ro*seri/myocar"itis
AS#$hronic- 7$% 9>>
iO G anti CD; #1 rituxima& inc response rates&O "odu$ar !o$$icu$ar $ymphomas pa$$iati2e *s$ow growing) present when
ad2,(4OMu$tip$e Mye$oma
aO Me$pha$an) prednisone *MP protoco$,iO (st $ine p$us &orte9omi& *;F proteasome inhi&itor down
regu$ates "A =1 path,&O (st $ine $ena$idomide G dexamethasonecO tem ce$$ transp$ant pts #.8ID a$%y$ating agents) me$pha$andO 6e!ractory/re$apsed d9 tha$idomide *w dexamethasone,eO .#D protoco$ *2incristine) doxoru&icin) dexamethasone, Gtha$idomide
(5O1reast CanceraO tage ( surgery a$one&O tage ; *node in2o$2ement,
iO CMA protoco$ cyc$ophosphamide) methotrexate) uorouraci$(O 6G add tamoxi!en
iiO A#C uorouraci$) doxoru&icin) cyc$ophosphamideiiiO Doxoru&icin G cyc$ophosphamide then A C uorouraci$)
epiru&icin) cyc$ophosphamidei2O Trastu9uma& *her;/neu G, w anthracyc$ine G taxane2O Tamoxi!en * 6 G, *add aromatase inhi&itors
anastro9o$e/$etro9o$e i! $ong term,2iO Toremi7ne newer agent used in 1r ca) 6 antagonist
cO tage B) 4 many same as a&o2e anthracyc$ines) taxanesiO #romatase inhi&itors) tamoxi!en
iiO ;nd
$ine exemestane a!ter tamoxi!en therapy(FOProstate CanceraO 0 6 agonists $eupro$ide) gosere$in agonists a$one or w antiandrogen
utamide) &ica$utamide) ni$utamide&O ;nd $ine aminog$utethimide G hydrocortidosne) %etocona9o$e G
hydrocortisone) hydrocortisone monocO ormone re!ractory mitoxantrone G prednisone
iO stramustine a$one or w/ etoposide or taxaneiiO Docetaxe$ G prednisone>>>>
('O82arian CanceraO tage ( cisp$atin) cyc$ophosphamide&O B/4 Q pac$itaxe$) car&op$atin
cO 6ecurrent topotecan 86 a$tretamine 86 doxoru&icin(JOTesticu$ar
aO Cisp$atin) etoposide) &$eomycin *P 1 protoco$, G 2in&$astine&O igh ris% cisp$atin) etoposide) i!o!s!amide
( OMa$ignant Me$anomaaO Dacar&a9ine) temo9o$omide) cisp$atin&O IA"a) I0; greater responsecO 16#A mutatuion 2emura!eni& *16#A inhi&itor,
; O1rain Cancer
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aO "itrosoureas&O PC. procar&a9ine G 2incristine G carmustine/$omustine *nitrosoureas,cO @$io&$astoma mu$ti!orme temo9o$omide G radiotherapy
iO 1e2aci9uma&;(O; nd ma$ignancies
aO #m$ *!rom a$%y$ating) epipodophy$$otoxins,
;;O ALL5 = IN5L Drug used concurrent$y with toxic anticancer agents toreduce rena$ precipitation o! urates
;BO E7NIS5NE-- Drug used in cancer therapy causes Cushing $i%e symptoms;4O AB,7 EGI%IN