Yellow are those that Dr. Der highlighted in lecture
Class
Prototype (generic Major Variants
and proprietary
names)
Alkylating
Agents
Nitrogen
Cyclophosphamide Methclorethamine
mustards
(Cytoxan, Neosar) (Mustargen)
Chorambucil
(Leukeran)
Alkylsulfonates
Ethylenimines
Nitrosoureas
Triazenes
Platinum
complex
Antimetabolites
Folate analogs
Busulfan
(Myleran)
Thiotepa
Carmustine
(BCNU, BiCNU)
Dacarbazine
(DTIC-Dome)
Cisplatin
(Platinol)
Methotrexate
(Folex, Mexate)
Mechanism of Action
Toxicity  dose
limiting (others)
Resistance
Misc.
Transfer of alkyl groups to
DNA  cross-linking 
impaired DNA replication
Myelosuppression
(Nausea, vomiting)
-Increased DNA
repair
-Increased
production of
glutathione 
inactivates drug
-Decreased
permeability of drug
-CCNS
-A prodrug that
requires activation
by hepatic cyc
P450
-Ovarian cancer,
neuroblastoma
uses
Lomustine
(CCNU, CeeNU)
Semustine
(methyl-CCNU)
Cross-links DNA  inhibits
DNA replication, RNA and
protein synthesis
Myelosuppression
(Nausea, vomiting)
-Increased DNA
repair
-Increased
production of
glutathione 
inactivates drug
-Decreased
permeability of drug
-Can alkylate
resting cells, but
cytotoxicity seen
only on division
-Highly lipid
soluble and can
penetrate into the
CNS  used for
brain tumors
Carboplatin
(Paraplatin)
-Thought to bind and crosslink DNA  inhibits both
DNA and RNA synthesis
Nephrotoxicity 
for cisplatin
Myelosuppression
 for carboplatin
-Diminished
transport
-Inactivation by
glutathione
-Enhanced repair by
unknown mechs
-CCNS  most
toxic at G1 and S
-Impt for treatment
of solid tumors
-Inhibits DHFR  prevents
formation of FH4  Inhibits
DNA, RNA, protein synthesis
Myelosuppression
(stomatitis,
erythema, rash,
urticaria, alopecia,
nausea, vomiting,
diarrhea)
-Increaed DHFR
levels
-Mutant DHFR with
decreased MTX
binding
-Decreased uptake
-CCS
-Toxicity can be
partially overcome
by use of
Leucovorin
rescue
-Used for ALL,
Burkitt’s
Purine analogs
Mercaptopurine
Thioguanine (6(6-MP, Purinethol) TG, Tabloid)
Pyrimidine
analogs
5-Fluorouracil (5FU, Efudex,
Adrucil)
Cytarabine (ara-C,
Cytosar-U)
Vinblastine
(Velban, Velsar)
Podophyllotoxins
Etoposide
(VePesid)
Taxines
Paclitaxel (Taxol)
Plant
Derivatives
Vinca alkaloids
Antibiotics
Anthracyclines
Doxorubicin
(Adriamycin)
lymphoma, breast
CA
-CCS
-Penetrate into tumor cells
and converted to unnatural
nucleotides by HGPRT 
inhibit many enzymes in
DNA, RNA synthesis
-Can be incorporated into
RNA and DNA  DNA
damage
-Requires intracellular
conversion to FdUMP 
inhibits Thymidylate
synthase  inhibits dTMP
production
-Also converted to 5-FUTP
 incorporated into RNA 
interferes with RNA function
-ara-C converted to AraCTP
 inhibits DNA polymerase
Myelosuppression
(nausea, vomiting,
diarrhea)
-Decreased HGPRT
activity
-5-FU = Nausea,
vomiting, diarrhea,
alopecia
-ara-C =
myelosuppression
-Increased synthesis
or altered affinity of
thymidylate
synthase
-Depletion of
enzymes that
activate 5-FU
-Deficiency of
enzyme that
activates ara-C
-CCS
Vincristine
(Oncovin,
Vincasar)
-Bind tubulin and prevent
polymerization  inhibit
mitotic spindle formation 
inhibit mitosis
-Decreased uptake
and retention
(MDR)
-CCS, M phase
specific
Tenoposide (VM26, Vumon)
-Binds topoisomerase II 
renders DNA susceptible to
irreversible double-strand
breaks  inhibits religation
-VBL 
myelosuppression
-VCR 
peripheral
neuropathy
-Myelosuppresion
(alopecia,
anaphylactic
reactions, nausea,
vomiting)
-Myelosuppression
-Decreased
accumulation
(MDR)
-CCS, S-G2
-Decreased
accumulation
(MDR)
-Mutations in
tubulin that prevent
binding
-CCS, M phase
-Myelosuppression
-Cardiac toxicity
due to oxygen
radical formation
-Increased efflux
(MDR)
-CCNS, maximal
activity at S and
G2
-Binds tubulin and promotes
polymerization 
stabilization of mitotic
spindle  cells frozen in
mitosis
Daunorubicin
(Cerubidine)
-Binds to topoisomerase II
and forms covalent topoIIDNA complexes  dsDNA
breaks
-Intercalate into DNA 
blocks DNA and RNA
synthesis
-Oxygen radical production
Actinomycins
Bleomycins
Mitomycins
Hormones
Anti-estrogens
Dactinomycin
(Actinomycin D,
Cosmegen)
Bleomycin
(Blenoxane)
-Fe(II)-bleomycin complex
forms  produces free
radicals  single- and
double-stranded DNA breaks
-Pulmonary
toxicity
-Myelosuppression
is rare
-Mechanisms
unknown
-CCS, cells
accumulate in G2
-Binds estrogen receptor 
inhibits its translocation to
nucleus and nuclear binding
 blocks transcriptional
activation of genes required
for growth
-Few toxic side
effects
-3-fold increased
risk for
endometrial cancer
-Hot flashes,
nausea, vomiting
-Several mechs.
proposed
-Loss of estrogen
receptor positive
cells
-CCNS
-Agonist of GnRH receptor
 chronic stimulation leads
to desensitization and
downregulation of receptor
function  inhibits release of
FSH and LH  reduced
testicular androgen synthesis
-Minimal side
effects 
impotence, hot
flashes, tumor
flare
-Inhibits ribonucleotide
reductase  inhibits
conversion of ribonucleotides
to deoxyribonucleotides 
inhibits DNA synthesis
-Does not need to enter tumor
cells to cause cell death
-Catalyzes deamination of
extracellular asparagines to
aspartate and ammonia 
certain tumors can’t
synthesize their own
asparagines
-Myelosuppression
-Hydroxyureainsesnsitive
reductase
-Increased reductase
levels
-Increaesd
expression of
asparagines
synthetase in tumor
-CCS, S-phase
specific
Mitomycin C
(Mutamycin)
Tamoxifen
(Nolvadex)
Gonatotropinreleasing
hormone agonists
Leuprolide
(Lupron)
Adrenocorticoids
Miscellaneous
Substituted urea
Prednisone
Enzymes
L-asparaginase
(Elspar)
Hydroxyurea
(Hydrea)
Goserelin
-Hypersensitivity
reactions, urticaria,
nausea, vomiting,
skin rashes, sever
anaphylactic
reactions
-No
myelosuppression,
alopecia, or GI
toxicity
Anti-Emetics
5-HT antagonists
D2-receptor
antagonists
Bone Marrow
Growth
Factors
Myeloid growth
factors
Signal
Transduction
Inhibitors
Monoclonal
antibodies
Kinase inhibitors
Ondansetron
(Zofran)
Prochlorperazine
(Compazine)
Metoclopramide
(Reglan)
G-CSF (filgrastim;
Neupogen)
GM-CSF
(sargramostim;
Leukine)
Trastuzumab
(Herceptin)
Cetuximab
(Erbitux)
Bevacizumab
(Avastin)
Gefitinib (Iressa)
Imatinib (Gleevec)
Erlotinib
(Tarceva)
-Trastuzumab  blocks the
growth promoting activity of
HER2 that is overexpressed
in some cancers (breast,
ovarian, etc.)
-Cetuximab  inhibitor of
mutated or overexpressed
EGFR
-Bevacizumab  blocks
VEGF stimulation of VEGF
receptor tyrosine kinase 
blocks angiogenesis
Gefitinib and Erlotinib 
Inhibitors of mutated or
overexpressed EGFR
-Imatinib  Blocks activity
of Bcr-Abl and Kit tyrosine
kinases
-Trastuzimab:
Mild, some cardiac
toxicity,
hypersensitivity
reactions
Cetuximab: Sever
infusion reactions
Bevacizumab:
Uncommon, but
include GI
perforation
-Trastuzimab: Loss
Her2 expression
Cetuximab: Loss of
EGFR expression
Bevacizumab:
Unknown
-Gefitinib: Mild;
severe interstitial
lung disease
-Imatinib: Mild;
serious and severe
problems include
liver problems,
fluid retention,
bleeding problems
-Gefitinib: Loss of
EGFR expression
-Imatinib: Mutation
of Bcr-Abl