Download MS2 Onc Chemo Table

Class
Drug
Chemistry
Nitrogen mustards:
cyclophosphamide
methclorethamine
chorambucil
Alkylsulfonates:
busulfan
cyclophosphamide: prodrug
requiring activation by hepatic
cytochrome p450 oxidase
Mechanism
Cell
Cycle
Ethylenimines:
thiotepa
Alkylating
Agents
Nitrosoureas:
carmustine
lomustine
semustine
Triazenes:
dacarbazine
high lipid solubility  entry into
CNS
Platinum complex:
cisplatin
carboplatin
inorganic metal complexes
DNA crosslinking  impaired DNA replication
 inhibits DNA synthesis
CCNS
Toxicity
Resistance
myelosuppression
Increased capability to repair DNA
lesions
nausea and vomiting (cisplatin,
dacarbazine, methclorethamine,
cyclophosphamide, lomustine,
carmustine)
increased risk of 2nd malignancies
Decreased permeability/uptake of
drug
Increased production of
glutathione (GSH) which
inactivates alkylating agent thru
conjugation
cisplatin only: renal toxicity
Procarbazine
Antimetabolites
Folate analogs:
methotraxate
acts as antagonist to folic acid
Purine analogs:
mercaptopurine (6MP)
thioguanine
require intracellular conversion
by HGPRT
Pyrimidine analogs:
5-Fluorouracil (5FU)
prodrugs that require
intracellular conversion to active
forms
blocks DHFR that converts folic acid to active
form  depressed DNA, RNA, and protein
synthesis
activated forms inhibit enzymes involved in
purine synthesis  decreased DNA/RNA
synthesis
can also be incorporated into DNA  DNA
damage
5-FdUMP inhibits thymidylate synthase 
thymineless death  inhibition of DNA
synthesis
MTX: Leukovorin rescue (folinic
acid)
CCS
myelosuppression
decreases in activating enzymes
others
inhibits DNA pol  inhibits DNA synthesis
cytarabine (ara-C)
S phase
Plant
Derivatives
Vinca alkaloids:
vinblastine
vincristine
structural analogs of periwinkle
plant
bind tubulin to prevent polymerization to
microtubules  blocks mitosis
Podophyllotoxins:
etoposide
tenoposide
root of mayapple
structural analog of
podophyllotoxin
binds and inhibits topoisomerase II  DNA
susceptible to irreversible ds breaks
Taxines:
paclitaxel (Taxol)
bark of pacific yew tree
binds to tubulin but promotes polymerization
and overstablization of microtubules  cells
frozen in mitosis
procarbazine: resistance
mechanism not known
decreased drug uptake
mutant DHFR with decreased
MTX binding
increased DHFR expression
decreased HGPRT activity
M
phase
vincristine: peripheral neuropathy
CCS
myelosuppression
decreased uptake/conversion to
active form
increased deactivation
decreased uptake and retention
(MDR)
binding mutation in tubulin
increased efflux (MDR)
mutation of topo II
S/G2
increased efflux (MDR)
binding mutations in tubulin
M
phase
Antibiotics
Anthracyclines:
doxorubicin
daunorubicin
most important newer anticancer
drugs
Actinomycins:
dactinomycin
Bleomycins:
bleomycin
Mitomycins:
mytomycin C
Hormones
Anti-estrogens:
tamoxifen
Gonatotropin-releasing
hormone agonists:
leuprolide
non-steroidal anti-estrogen
synthetic peptide analogs of
GnRH (LHRH)  100 fold
more potent
Adrenocorticoids:
prednisone
Miscellaneous
formation of covalent topo II – DNA complexes
to prevent relegation
intercalate into DNA  block DNA/RNA
synthesis
cause production of O2 radicals  DNA strand
breaks, damage tumor and cardiac tissues
intercalation into DNA  disrupts RNA/DNA
synthesis
max at
S/G2
DNA strand breaks via O2 radical formation
CCNS
myelosuppression
increased efflux (MDR)
cardiac toxicity by O2 radical
formation
bone marrow depression
increased efflux (MDR)
CCS
pulmonary toxicity
unclear
NOT MDR
G2
myelosuppression rare
cross-links DNA
CCNS
myelosuppression
binds estrogen receptor
CCNS
among least toxic
side effects similar to those of
estrogen (hot flashes, nausea, etc)
3-fold increased potential for
endometrial cancer
nausea and vomiting
loss of receptor expression
no acute
delayed include fluid retention,
hypertension, diabetes, increased
susceptibility to infection
myelosuppression
loss or mutation of receptor
hypersensitivity rxns
increased capacity of tumor cell to
synthesize asparagines
confined to palliative treatment of estrogen
dependent, estrogen receptor positive breast
cancer
initially agonists
continual treatment leads to downregulation of
receptor and loss of stimulation  reduced
testicular androgen synthesis (decrease
testosterone levels)
treat prostate cancer
stimulates receptor function  production of
specific enzymes
Hydroxyurea
simple derivative of urea
inhibits ribonucleotide reductase  depletes
intracellular pools of deoxyribonucleotides 
block DNA synthesis
CCS
L-Asparaginase
purified from bacterial strains
converts blood asparagines into aspartic acid 
some tumors require exogenous asparagines in
blood to survive (normal cells can synthesize
their own)
inhibition of protein synthesis
CCS
increase in ribonucleotide
reductase
S phase
G1