Drug Class
Drug Name(s)
Cell Cycle
Specificity
S Phase
Mecanism of Action
Antimetabolites (folate
antagonists)
Methotrexate,
Pemetrexed
Pyrimidine antagonist
5-FU, Capecitabine
S Phase
Inhibits thymydilate
synthase to prevent
nucleotide synthesis
and therefore DNA
synthesis
Liver, head/neck,
Ovarian, Cervical
cancers
Pyrimidine Antagonist
Cytarabine (Ara-C)
S Phase
AML, ALL, CML, CNS
leukemia, NHL
Pyrimidine Antagonist
Gemcitabine
S Phase
Pyrimidine Antagonist
Azacitidine,
Decitabine
S Phase
Purine Antagonist
Fludarabine,
Cladribine,
Pentostatin
S Phase
Competitively inhibits
DNA polymerase and
terminates DNA
elongation by
incorporation
Incorporates into the
DNA strand and
prevents elongation
and repair
Hypomethylation of
DNA with some direct
toxicity on abnormal
cells
Adenosine analogs
that inhibit DNA
synthesis and repair
& RNA function
Purine Antagonist
6-mercaptopurine, 6TG
S Phase
ALL, CML, AML, NHL
Antimetabolites
Hydroxyurea
S Phase
Antimicrotubules/
vinca alkaloids.
(Metabolized by
CYP450)
Vincristine,
Vinblastine,
Vinorelbine
Metaphase
Converted to active
form by HGPRT
(purine salvage
enzyme) Inhibits denovo purine
synthesis.
Inhibits
ribonucleotide
reductase leading to
decreased DNA
synthesis
Binds to tubulin and
inhibits microtubule
assembly which leads
to cell arrest
Taxanes
(Metabolized by
CYP450)
Paclitaxel, docetaxel,
abraxane (albumin
bound paclitaxel)
Metaphase
Enhances tubulin
cross linking which
blocks normal cell
reproduction
Multiple solid
tumors
Epothilones-LOW
SUSCEPTIBILITY TO
RESISTANCE
Ixabepilone
G2-M
Arrest
Multidrug resistant
metastatic breast
cancer
Asparaginase
G1
Irinotecan,
topotecan
G2
Binds B tubulin to
promote proliferation
and prevent
breakdown of mitotic
spindles
Hydrolyzes Lasparagine causing
dysfunctional protein
synthesis
Stabilizes a cleavable
topoisomerase1-DNA
complex (ATP
independent) leading
to SS DNA strand
Topoisomerase
Inhibitor
(camptothecin
analogs)
Inhibits DHFR (blocks
DNA synthesis by
inhibiting THF
production).
Pemetrexed also
inhibits thymydilate
synthase.
Specific Indications
(if any)
Multiple
malignancies
(choriocarcinoma,
ALL, breast cancer,
lung cancer, NHL),
autoimmune
disorders, abortion
Important Side
Effects
Myelosuppression
(give Leucovorin to
alleviate severe BM
suppression),
hepatotoxicity, renal
toxicity.
*IT Admin: Causes
arachnoiditis and
chronic demyelinating
encephalopathy.
Myleosuppression. In
those with
dihydropyrimidine
dehydrogenase
deficiency, life
threatening toxicity
can occur
Myelosuppression,
cerebellar dysfunction
(with high doses)
Bladder, breast,
ovarian,
mesothelioma,
NSCLC
MDS
Myelosuppression
CLL, NHL, AML, Hairy
Cell Leukemia
Myelosuppression
w/OI, tumor lysis
syndrome, peripheral
neuropathy
(fludarabine),
Myelosuppression.
When given with
allopurinol can cause
overdose. VOD
(severe liver failure)
Resistance
Mechanisms
Drug efflux pump
(MDR)
Myelosuppression,
cardiac complications
(decitabine)
AML, sickle cell
anemia
Myelosuppression
Multiple
hematologic
malignancies and
some solid tumors
Peripheral
neuropathy,
myelosuppression, if
given IT causes severe
fatal ascending
paralysis.
Hypersensitivity
Reactions (decreased
with use of abraxane),
fluid retention,
peripheral
neuropathy
Peripheral
neuropathy, alopecia
ALL
Hypersensitivity
reactions, decreased
clotting factors
Ovarian cancer
(topotecan),
colorectal cancer
(irinotecan)
Myelosuppression,
dose limiting diarrhea.
HGPRT Deficiency
Efflux Pump
(MDR), alterations
in  and β tubulin
Efflux Pump
(MDR)
LOW
SUSCEPTIBILITY
TO MDR
Topoisomerase
alterations, MDR.
Topoisomerase
Inhibitor
(Epipodophyllotoxinsplant alkaloid)
Etoposide
G2
Topoisomerase
Inhibitor
Mitoxantroene
G2
Anthracyclines
(topoisomerase
inhibitor)
Doxorubicin, Doxil
(liposomal
doxorubicin)
Danorubicin,
Epirubicin, Idarubicin
G2
Alkylating Agents
(Platinums)
Cisplatin,
Carboplatin,
Oxaliplatin
Nonspecific
Alkylating Agents
(Nitrogen Mustards)
Cyclophosphamide,
Ifosfamide,
Melphalan,
Chlorambucil
Nonspecific
Alkylating Agents
(nitrosureas)
Alkylating Agents
Carmustine
Nonspecific
Busulfan
Nonspecific
Non-classical
Alkylating Agent
Temozolomide
Nonspecific
Antitumor Antibiotic
Bleomycin
G2
Arsenic Trioxide
Arsenic Trioxide
Nonspecific
All-trans retinoic acid
(ATRA)
Hormonal Agents
ATRA
N/A
Tamoxifen
N/A
Hormonal Agents
Fulvestrant
N/A
Hormonal Agents
Anastrozole,
Letrozole,
Exemestane
N/A
Hormonal Agents
Leuprolide, Goserelin
N/A
Hormonal Agents
Bicalutimide,
Nilutamide,
Flutamide
N/A
breakage upon
replication
Inhibits
topoisomerase II (ATP
dependent) leading to
DS DNA strand
breakage
Inhibits
topoisomerase II
causing cross linking
and DS DNA breaks
Inhibits
topoisomerase II,
intercalates between
base pairs disrupting
DNA and RNA
synthesis, produces
oxygen radicals, and
disrupts ion and fluid
balance
Alkylating agent that
cross links and
alkylates DNA. Causes
fragmentation by
repair enzymes and
prevention of DNA &
RNA synthesis.
Alkylating agent that
cross links and
alkylates DNA. Causes
fragmentation by
repair enzymes and
prevention of DNA &
RNA synthesis.
Alkylating agent that
can cross the BBB
Alkylating agent
Methylates guanine
residues preventing
DNA and protein
synthesis
Causes production of
oxygen free radicals
that damage DNA
Causes apoptosis of
cells
Induces maturation of
blasts in APL
Competitive estrogen
receptor antagonist
that blocks the effects
of estrogen in tumor
cells while
potentiating normal
estrogen function
elsewhere in the body
ER antagonist
Aromatase inhibitor
blocks the
transformation of
testosterone into
estrogen
GHRH Antagonists
Androgen receptor
blocker
Multiple
malignancies
Dose limiting
myelosuppression,
secondary AML
Refractory prostate
cancer, AML
Bluish sclera, urine,
and fingernails
Dano: ALL, AML
Doxo: Multiple
hematologic and
solid tumors
Arrhythmias,
cardiomyopathy,
pericarditis, CHF.
Cardiac sideFx be
decreased by
administration of
dexrazoxane.
Efflux Pump
(MDR), point
mutations on
topoisomerase II,
inactivation of
superoxide free
radicals
Multiple solid
tumors (primarily
genitourinary and
gastric malignancies)
Peripheral
neuropathies,
tinnitus, renal failure,
SIADH, metallic taste
Impaired influx or
enhanced efflux
pumps, cytosolic
drug inactivation,
DNA repair,
altered apoptotic
processes
Breast, Ovarian, NHL,
CLL, MM,
Lymphomas
Hemorrhagic cystitis,
myelosuppression
Brain tumors
Myelosuppression,
pulmonary fibrosis
Myelosuppression,
hepatotoxicity,
pulmonary fibrosis
Leukopenia,
thrombocytopenia
Bone marrow
transplant
GBM
Testicular cancers
Pulmonary fibrosis
APL
Prolonged QT
syndrome
Vitamin A toxicity
APL
Estrogen receptor +
breast cancers,
osteoporosis
Endometrial cancer,
thromboembolism,
hot flashes, vaginal
bleeding
Metastatic ER+
breast cancer
ER+ breast cancer
Hot flashes,
arthralgias, headache
Hot flashes,
arthralgias, headache
Breast and prostate
cancers
Hot flashes,
impotence, decreased
libido,
Decreased libido,
gynecomastia,
myalgias,
hepatotoxicity
Prostate cancer
Topoisomerases are enzymes that unwind and wind DNA, in order for DNA to control the synthesis of proteins, and to facilitate DNA replication
Topoisomerase I

Acts on one strand of DNA

Removes negative supercoils

No involvement in DNA replication

Expression is continuous during G2 phase of the cell cycle and in
quiescent cells

ATP independent
Topoisomerase II

Acts on both strands of DNA

Removes positive supercoils

Involved in DNA replication

Expression increases during S phase of the cell cycle & is almost absent in qu
cells

ATP dependent