Indirect DNA-Interacting Agents

Antimetabolites
Deoxycoformycin 4 mg/m
2
IV every
other week

Nausea
Immunosuppression
Neurologic
Renal
Excretes in urine
Reuce ose for renal
failure
Inhi!its aenosine
eaminase
"#$ercaptopurine %& mg/m
2
'(
or up &)) mg/m
2
'(
*high ose+
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,iver
Nausea
Varia!le !ioavaila!ility
$eta!oli-e !y xanthine
oxiase
Decrease ose with
allopurinol
Increase toxicity with
thiopurine
methyltransferase
eficiency
"#.hioguanine 2/0 mg/kg per ay for
up to 0/4 weeks
$arrow
,iver
Nausea
Varia!le !ioavaila!ility
Increase toxicity with
thiopurine
methyltransferase
eficiency
1-athioprine 2/& mg/kg per ay $arrow
Nausea
,iver
$eta!oli-es to "$'3
therefore reuce ose
with allopurinol
Increase toxicity with
thiopurine
methyltransferase
eficiency
2#
4hloroeoxyaenosine
)5)6 mg/kg per ay 7
x% as continuous
infusion
$arrow
Renal
8ever
Nota!le use in hairy cell
leukemia
9yroxyurea 2)/&) mg/kg *lean
!oy weight+ '( 7
or 2/0 g/
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Nausea
Decrease ose with renal
failure
1ugments antimeta!olite
effect
$ucositis
:kin changes
Rare renal3 liver3
lung3 4N:
$ethotrexate 2&/0) mg '( or I$ 7
x0/&
or 0) mg IV ays 2
an ;
or 25&/22 g/m
2
per ay
*with leucovorin+
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,iver/lung
Renal tu!ular
$ucositis
Rescue with leucovorin
Excrete in urine
Decrease ose in renal
failure
N:1IDs increase renal
toxicity
&#8luorouracil 0%& mg/m
2
IV 7 x&
or ")) mg/m
2
IV ays
2 an ;
$arrow
$ucositis
Neurologic
:kin changes
.oxicity enhance !y
leucovorin
Dihyropyrimiine
ehyrogenase
eficiency increases
toxicity
$eta!oli-es in tissues
4apecita!ine ""& mg/m
2
!i
continuous< 22&)
mg/m
2
!i 2 weeks on/
2 off< ;26 mg/m
2
!i 2
weeks on/ 2 off = ")
mg/ leucovorin

Diarrhea
9an#foot synrome
'rorug of &8> ue to
intratumoral meta!olism
4ytosine ara!inosie 2)) mg/m
2
per ay 7
x% !y continuous
infusion
or 2/0 g/m
2
ose IV
!olus
$arrow
$ucositis
Neurologic *high
ose+
4on?unctivitis *high
ose+
Noncariogenic
pulmonary eema
Enhances activity of
alkylating agents
$eta!oli-es in tissues !y
eamination
1-acytiine %&) mg/m
2
per week
or 2&)/2)) mg/m
2
per
ay x&/2) *!olus+ or
*continuous IV+
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Nausea
,iver
Neurologic
$yalgia
>se limite to leukemia
1ltere methylation of
DN1 alters gene
expression
@emcita!ine 2))) mg/m
2
IV weekly
x%

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Nausea
9epatic
8ever/Aflu synromeA

8luara!ine phosphate 2& mg/m
2
IV 7 x&

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Neurologic
,ung
Dose reuction with renal
failure
$eta!oli-e to 8#ara
converte to 8#ara 1.' in
cells !y eoxycytiine
kinase
1sparaginase 2&3))) I>/m
2
70/4
weeks
or "))) I>/m
2
per ay
7o for 0/4 weeks
or 2)))/2))) I>/m
2

for 2)/2) ays
'rotein synthesis
4lotting factors
@lucose
1l!umin
9ypersensitivity
4N:
'ancreatitis
9epatic
Blocks methotrexate
action
'emetrexe 2)) mg/m
2
70 weeks

1nemia
Neutropenia
.hrom!ocytopenia
:upplement folate/B22
4aution in renal failure