Chapter 081. Principles of Cancer Treatment (Part 11) potx

Chapter 081. Principles of
Cancer Treatment
(Part 11)
Table 81-2 Commonly Used Cancer Chemotherapy Agents

Drug Exam
ples of Usual
Doses
Toxicity Interactions,
Issues
Direct DNA-Interacting Agents
Alkylators

Cyclophospha 400–
2000 mg/m
2

Marrow (relative
Liver
metabolism required
mide IV
100
mg/m
2
PO qd

platelet sparing)
Cystitis
Common
alkylator
a

Cardiac (high
dose)
to activate to
phosphoramide
mustard + acrolein
Mesna
protects against
"high-
dose" bladder
damage
Mechloretha
mine
6
mg/m
2
IV day
1 and day 8
Marrow
Vesicant
Nausea
Topical use in
cutaneous lymphoma

Chlorambucil

1–3
mg/m
2
qd PO

Marrow
Common
alkylator
a


Melphalan 8
mg/m
2
qd x 5,
PO
Marrow (delayed
nadir)
Decreased
renal function delays
clearance
GI (high dose)
Carmustine
(BCNU)
200
mg/m
2
IV
150
mg/m
2
PO
Marrow (delayed
nadir)

GI, liver (high
dose)
Renal

Lomustine
(CCNU)
100–
300 mg/m
2

PO
Marrow (delayed
nadir)

Ifosfamide 1.2
g/m
2
per day
qd x 5 +
mesna
Myelosuppressiv
e
Bladder
Neurologic
Metabolic
acidosis
Isomeric
analogue
of
cyclophosphamide

More lipid
soluble
Greater
activity vs testicular
Neuropathy
neoplasms and
sarcomas
Must use
mesna
Procarbazine 100
mg/m
2
per
day qd x14
Marrow
Nausea
Neurologic
Common
alkylator
a

Liver and
tissue metabolism
required
Disulfiran-
like effect with
ethanol
Acts as
MAOI
HBP after

tyrosinase-rich foods

Dacarbazine
(DTIC)
375
mg/m
2
IV day
1 and day 15
Marrow
Nausea
Metabolic
activation
Flulike
Temozolomid
e
150–
200 mg/m
2
qd
x 5 q28d or

75 mg/m
2
qd
x 6–7 weeks
Nausea/vomiting

Headache/fatigue

Constipation
Infrequent
myelosuppression
Altretamine
(formerly
hexamethylmelamin
e)
260
mg/m
2
per
day qd x14–
21 as 4
divided oral
doses
Nausea
Neurologic
(mood swing)
Neuropathy
Marrow (less)
Liver
activation
Barbiturates
enhance/cimetidine
diminishes
Cisplatin 20
mg/m
2
qd x5
IV 1 q3–

4
weeks or

100–200
mg/m
2
per
Nausea
Neuropathy
Auditory
Marrow platelets
Maintain high
urine flow; osmotic
diuresis, monitor
intake/output K
+
,
Mg
2+

dose IV q3–
4
weeks
> WBCs
Renal Mg
2+
, Ca
2+

Emetogenic—

prophylaxis needed
Full dose if
Cr
Cl > 60 mL/min
and tolerate fluid
push
Carboplatin 365
mg/m
2
IV
q3–
4 weeks
as adjusted
for CrCl
Marrow platelets
> WBCs
Nausea
Renal (high dose)

Reduce dose
according to CrCl: to
AUC of 5–
7 mg/mL
per min [AUC =
dose/(CrCl + 25)]
Oxaliplatin 130
mg/m
2
q3
weeks over 2

h or
85
mg/m
2
q2
weeks
Nausea
Anemia
Acute
reversible
neurotoxicity;
chronic sensory
neurotox cumulative
with dose; reversible
laryngopharyngeal
spasm
Antitumor
antibiotics

Bleomycin 15–25
mg/d qd x5
IV bolus or

continuous
IV
Pulmonary
Skin effects
Raynaud's
Hypersensitivity
Inactivate by

bleomycin hydrolase
(decreased in
lung/skin)
O
2
enhances
pulmonary toxicity
Cisplatin-
induced decrease in
CrCl may increase
skin/lung toxicity
Reduce dose
if CrCl < 60 mL/min

Actinomycin 10–15
µg/kg
per day
Marrow Radiation
D
qd x5 IV
bolus
Nausea
Mucositis
Vesicant
Alopecia
recall
Mitomycin C 6–10
mg/m
2
q6

weeks
Marrow
Vesicant
Hemolytic-
uremic syndrome
Lung
CV—heart
failure
Treat
superficial bladder
cancers by
intravesical infusion
Delayed
marrow toxicity
Cumulative
marrow toxicity
Etoposide
(VP16-213)
100–
150 mg/m
2

IV qd x3–5d
or
50
Marrow (WBCs
> platelet)
Alopecia
Hepatic
metabolism—renal

30%
Reduce doses
mg/m
2
PO qd
x21d
or
up
to 1500
mg/m
2
per
dose (high
dose with
stem cell
support)
Hypotension
Hypersensitivity
(rapid IV)
Nausea
Mucosit
is (high
dose)
with renal failure
Schedule-
dependant (5 day
better than 1 day)
Late
leukemogenic
Accentuate

antimetabolite action

Topotecan 20
mg/m
2
IV
q3–
4 weeks
over 30 min
or 1.5–
3 mg/m
2
q3–
4
weeks over
24 h
or
0.5
mg/m
2
per
Marrow
Mucositis
Nausea
Mild alopecia
Reduce dose
with renal failure
No liver
toxicity
day over 21

days
Irinotecan
(CPT II)
100–
150 mg/m
2

IV over 90
min q3–
4
weeks
or
30
mg/m
2
per
day over 120
h
Diarrhea: "early
onset" with cramping,
flushi
ng, vomiting; "late
onset" after several
doses
Marrow
Alopecia
Nausea
Vomiting
Pulmonary
Prodrug

requires enzymatic
clearance to active
drug "SN 38"
Early diarrhea
likely due to biliary
excretion
Late diarrhea,
use "high-
dose"
loperamide (2 mg
q2–4 h)
Doxorubicin
and daunorubicin
45–60
mg/m
2
dose
q3–4 weeks
or 10–
Marrow
Mucositis
Alopecia
Heparin
aggregate;
coadministration
increases clearance
30 mg/m
2

dose q week

or
continuous-
infusion
regimen
Cardiovascular
acute/chronic
Vesicant
Acetaminoph
en, BCNU incr
ease
liver toxicity
Radiation
recall
Idarubicin 10–15
mg/m
2
IV q 3
weeks
or
10
mg/m
2
IV qd
x3
Marrow
Cardiac (less
than doxorubicin)
None
established
Epirubicin 150

mg/m
2
IV q3
weeks
Marrow
Cardiac
None
established
Mitoxantrone

12
mg/m
2
qd x3
Marrow
Cardiac (less
Interacts with
heparin
or 12–
14 mg/m
2
q3
weeks
than doxorubicin)
Vesicant (mild)
Blue urine,
sclerae, nails
Less alopecia,
nausea than
doxorubicin

Radiation
recall
Indirect DNA-Interacting Agents
Antimetaboli
tes

Deoxycoform
ycin
4
mg/m
2
I
V
every other
week
Nausea
Immunosuppressi
on
Neurologic
Renal
Excretes in
urine
Reduce dose
for renal failure
Inhibits
adenosine deaminase

6- 75 Marrow Variable
Mercaptopurine mg/m
2

PO
or
up
500 mg/m
2

PO (high
dose)
Liver
Nausea
bioavailability
Metabolize b
y
xanthine oxidase
Decrease dose
with allopurinol
Increased
toxicity with
thiopurine
methyltransferase
deficiency
6-
Thioguanine
2–3
mg/kg per
day for up to
3–4 weeks
Marrow
Liver
Nausea

Variable
bioavailability
Increased
toxicity with
thiopurine
methyltransferase
deficiency
Azathioprine 1–5
mg/kg per
day
Marrow
Nausea
Liver
Metabolizes
to 6MP, therefore
reduce dose with
allopurinol
Increased
toxicity with
thiopurine
methyltransferase
deficiency
2-
Chlorodeoxyadenosi
ne
0.09
mg/kg per
day qd x7 as
continuous
infusion

Marrow
Renal
Fever
Notable use in
hairy cell leukemia
Hydroxyurea 20–50
mg/kg (lean
body weight)
PO qd
Marrow
Nausea
Mucositis
Decrease dose
with renal failure
Augments
or 1–
3
g/d
Skin changes
Rare renal, liver,
lung, CNS
antimetabolite effect

Methotrexate 15–30
mg PO or IM
qd x3–5
or
30
mg IV days 1
and 8

or 1.5–
12 g/m
2
per
day (with
leucovorin)
Marrow
Liver/lung
Renal tubular
Mucositis
Rescue with
leucovorin
Excreted in
urine
Decrease dose
in renal failure
NSAIDs
increase renal
toxicity
5-Fluorouracil

375
mg/m
2
IV qd
x5
or
600
Marrow
Mucositis

Neurologic
Toxicity
enhanced by
leucovorin
Dihydropyrim
mg/m
2
IV
days 1 and 8
Skin changes
idine dehydrogenase
deficiency increases
toxicity
Metabolizes
in tissues
Capecitabine 665
mg/m
2
bid
continuous;
1250 mg/m
2

bid 2 weeks
on/ 1 off; 829
mg/m
2
bid 2
weeks on/ 1
off + 60 mg/d

leucovorin
Diarrhea
Hand-foot
syndrome
Prodrug of
5FU due to
intratumoral
metabolism
Cytosine
arabinoside
100
mg/m
2
per
day qd x7 by
continuous
Marrow
Mucositis
Neurologic (high
Enhances
activity of alkylating
agents
infusion
or 1–
3
g/m
2
dose IV
bolus
dose)

Conjunctivitis
(high dose)
Noncardiogenic
pulmonary edema
Metabolizes
in tissues by
deamination
Azacytidine 750
mg/m
2
per
week
or
150–200
mg/m
2
per
day x5–
10
(bolus) or
(continuous
IV)
Marrow
Nausea
Liver
Neurologic
Myalgia
Use limited to
leukemia
Altered

methylation of DNA
alters gene
expression
Gemcitabine 1000
mg/m
2
IV
Marrow
Nausea

weekly x7 Hepatic
Fever/"flu
syndrome"
Fludarabine
phosphate
25
mg/m
2
IV qd
x5
Marrow
Neurologic
Lung
Dose
reduction with renal
failure
Metabolized
to F-
ara converted to
F-

ara ATP in cells
by deoxycytidine
kinase
Asparaginase

25,000
IU/m
2
q3–
4
weeks
or
6000 IU/m
2

per day qod
Protein synthesis

Clotting factors
Glucose
Albumin
Hypersensitivity
Blocks
methotrexate action
for 3–4 weeks

or
1000–2000
IU/m
2

for 10–
20 days
CNS
Pancreatitis
Hepatic
Pemetrexed 200
mg/m
2
q3
weeks
Anemia
Neutropenia
Thrombocytopen
ia
Supplement
folate/B
12

Caution in
renal failure
Antimitotic
agents

Vincristine 1–1.4
mg/m
2
per
week
Vesicant
Marrow

Neurologic
GI:
Hepatic
clearance
Dose
reduction for
bilirubin >1.5 mg/dL

ileus/constipation;
bladder hypotoxicity;
SIADH
Cardiovascular
Prophylactic
bowel regimen
Vinblastine 6–8
mg/m
2
per
week
Vesicant
Marrow
Neurologic (le
ss
common but similar
spectrum to other
vincas)
Hypertension
Raynaud's
Hepatic
clearance

Dose
reduction as with
vincristine
Vinorelbine 15–30
mg/m
2
per
week
Vesicant
Marrow
Allergic/broncho
Hepatic
clearance
spasm (immediate)
Dyspnea/cough
(subacute)
Neurologic (less
promin
ent but similar
spectrum to other
vincas)
Paclitaxel 135–
175 mg/m
2

per 24-
h
infusion
or
175

mg/m
2
per 3-
h infusion
or
140
mg/m
2
per
96-h infusion

or
250
Hypersensitivity
Marrow
Mucositis
Alopecia
Sensory
neuropathy
CV conduction
disturbance
Nausea—
Premedicate
with steroids, H
1
and
H
2
blockers
Hepatic

clearance
Dose
reduction as with
vincas
mg/m
2
per
24-
h infusion
plus G-CSF
infrequent
Docetaxel 100
mg/m
2
per 1-
h infusion q3
weeks
Hypersensitivity
Fluid retention
syndrome
Marrow
Dermatologic
Sensory
neuropathy
Nausea
infrequent
Some stomatitis
Premedicate
with steroids, H
1

and
H
2
blockers
Estramustine
phosphate
14
mg/kg per
day in 3–
4
Nausea
Vomiting

divided doses
with water >2
h after meals
Avoid
Ca
2+
-rich
foods
Diarrhea
CHF
Thrombosis
Gynecomastia
NAB-
Paclitaxel (protein
bound)
260
mg/m

2
q3
weeks
Neuropathy
Anemia
Neutropenia
Thrombocytopen
ia
Caution in
hepatic insufficiency

Molecularly Targeted Agents
Imatinib 400
mg/d,
continuous
Nausea
Periorbital edema

Myelosuppres
sion not frequ
ent in
solid tumor
indications
Tretinoin 45
mg/m
2
per
day until
complete
response +

anthrocycline
-based
regimen in
APL
Teratogenic
Cutaneous
APL
differentiation
syndrome:
pulmonary
dysfunction/infiltrate
, pleural/pericardial
effusion, fever
Bexarotene 300–
400 mg/m
2

per day,
continuous
Hypercholesterol
emia
Hypertriglyceride
mia
Cutaneous
Teratogenic
Central
hypothyroidism
Gemtuzumab
ozogamicin
9

mg/m
2
over 2
Neutropenia
Thrombocytopen
Postinfusion
syndrome: fever,
h q2 weeks,
usually
followed by
chemotherapy
or marrow
transplant
ia
Hepatic
chills, hypotension
Rare hepatic
venoocclusive
disease
Mucositis
uncommon
Denileukin
diftitox
9–18
µg/kg per day
x 5 d q 3 wk
Nausea/vomiting

Chills/fever
Asthenia

Hepatic
Acute
hypersensitivity:
hypotension,
vasodilation
, rash,
chest tightness
Vascular leak:
hypotension, edema,
hypoalbuminemia,
thrombotic events
(MI, DVT, CVA)
Gefitinib 250
mg PO per
Rash
In U.S., only
with prior