7/25/2019 Temozolomide and Irinotecan Synergy
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A summary of the synergistic antitumor eect of irinotecan
following temozolomideadministration
Sean Green, PharmDOctober 13, 2013
Irinotecan is a camptothecan antineoplastic agent which exerts
its efects through
inhibition o the topoisomerase I en!"me# $" stabili!ing the
co%alent bon&s between D'( an&the replication or),
irinotecan is able to halt S*phase D'( replication an& exert
clinicall"signi+cant anti*tumor efects against a %ariet" o
neoplasms, inclu&ing a&ult gastrointestinal,lung, brain
an& g"necologic cancers an& pe&iatric
rhab&om"osarcoma an& neuroblastoma#Separatel",
temo!olomi&e, the pro&rug o monometh"l
tria!enoimi&a!ole carboxami&e -./I,has &emonstrate&
acti%it" against high*gra&e pe&iatric gliomas through its
mechanism o O*guanine meth"lation# hile irinotecan is
tra&itionall" gi%en as a single intra%enous agent in&oses o
124 to 340mg5m2e%er" 1 to 3 wee)s, an& temo!olomi&e is
a&ministere& as 200 to214mg5m2orall" -&ue to its
excellent bioa%ailabilit" or 4 &a"s in each 26 &a" c"cle,
recentpreclinical an& human &ata ha%e suggeste& a
s"nergistic action between these two agents whenirinotecan is
a&ministere& ollowing temo!olomi&e#
In 2000, 78 Patel an& colleagues examine& the
combination o temo!olomi&e an&irinotecan against a
malignant glioma xenograt in mice# Since the two &rugs ha&
pre%iousl"been pro%en to be acti%e against central ner%ous s"stem
malignancies in the past, the" wishe&to create a regimen, which
coul& potentiall" ha%e greater results# $" a&ministering
0#1 o the109 lethal &ose -:D10 o temo!olomi&e on &a" 1
an& 0#1 o the :D10 o irinotecan on &a"s 1through 4 an&
6 through 11, the" oun& a response greater than the
a&&iti%e efects o the twoagents, e%en when irinotecan
a&ministration was &ela"e& b" 3 to 4 &a"s# ;owe%er,
when theexperiment was re%erse& b" gi%ing 0#4 o the irinotecan
:D10 on &a" 1 ollowe& b" 0#1 o the :D10o temo!olomi&e
at 3 hours, 4 hours an& 4 &a"s post*irinotecan, less
acti%it" was seen than witheither agent alone# Similar results were
achie%e& b" P8 ;oughton et al, who assesse& 4 &a"s
otemo!olomi&e ollowe& b" 4 &a"s o irinotecan gi%en in
three 21*&a" c"cles o%er eight wee)s tomice with neuroblastoma,
rhabom"osarcoma an& glioblastoma xenograts# / an&
neurolblastoma, respecti%el"#
