pharm 54 chemo

8/10/2019 Pharm 54 Chemo

1/23

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


2/23

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


3/23

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


4/23

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


5/23

uorouraci$AU,

anal *reast )gastroesophagea$) head/nec%)hepatoce$$u$ar

stomach

pancreas-*asal cellcarcinoma(to ica $,

t(/;( (5min

thymi"inesynthase-incor ates


6/23

-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"@

-


7/23

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


8/23

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


9/23

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


10/23

$eu%emiaC00$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"


11/23

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


12/23

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#


13/23

&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?


14/23

*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


23/23

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

pharm 54 chemo

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