Anti- ca.

Drugs: alkylating agents, anti metabolites, and antitumor abiotics

Dactinomycin

ANTI-BIOTICS against ca.

Doxorubicin and Daunorubicin

Bleomycin

CCNS/CCS

CCNS

Mech of action

Forms complex between G-C so

now DNA dep RNA polymerase
cant work

Resistance

Administration

1. efflux pump= P-glycoprot

2. DNA repair
Combo with surgery for Wilms
tumor
Combo with MTX for gestational
choriocarcinoma
Iv

Pharmacokinetics

Bile and urine excretion

Bile and urine excretion

Kidneys

sideefx

BM depression, stomatitis,
alopecia

Cardiotoxicity

Pulmonary toxicity ( pneumonitis and

death), fever because doesnt get inactivated
in the lung as good as other parts of the body

Clinical uses

Extra notes

CCS
1. intercalation in the DNA blocking
DNA RNA syn
2. membrane disruption
3. O2 radical production by P-450
which damagese DNA
efflx by P-glycoprot
HD (ABVD regimen)
Breast lung
ALL, AML
Kaposi sarcoma
Iv

Reverse sideefx by dexrazoxane=

zinecard, this chelates Fe

Interacts with topoisomerase II

Cells accumulate and get stuck in G2 phase
and mitosis
1. efflux
2. DNA repair
Testicular
Squamous cell carcinoma
HL
s.c., im, iv

CCNS/CCS
Mech of action

Resistance

Clinical uses

Administration
Pharmacokinetics
sideefx

Extra notes

ALKYLATING AGENTS against ca.

all CCNS
Mechlorethamine
Cyclophosphamide and
Nitrosoureas (NU)=
nitrogen mustard
ifosfamide nitrogen
Carmustine and lomustine
mustards
CCNS
CCNS
CCNS
Reactive intermediate,
Breakdaown to active
can x BBB
alkylates the guanine
compound phosphoramide
alkylating metabolites
residue of DNA molecule
mustard and acrolein for
which will cause cross
cytoxicity upon the DNA
linking of DNA
inhibiting syn
1. perm of drug
1. perm of drug
1. rxn w/ thiols
2. conjugate thioles like
2. conjugate thioles like
glutathion
glutathione
2. DNA repair
3. DNA repair
3. DNA repair
HL (part of MOPP)
Burkitts
Good for Brain tumors
Breast, ovarian, NHL, CLL, Also HD, NHL
CML, ANLL, ALL,
inulinomas
Myeloma, neuro and
retinoblastomas
Iv
Unique: taken orally
Carmustine iv
Lomustine oral
Excreted in feces via bile
kidney
Also urine by GF
BM depression, can cause
Hematopoeitic depression
latency for vs
Hemorrhagic cystitis due to CNS depression
GI disturbances
acrolein
Renal toxicity
Pulmonary fibrosis
Use iv MENSNAwhich will
inactivate the toxic
compounds

Busulfan
CCNS

CML @ low doses

Myelosuppression
Pulm fibrosis
Cytotic actins dont appear
to exted to either the
lymphoid tissue or GI

MTX
CCNS/CCS
Mech of
action

CCS (on S phase)

~ folate inhibits
dihydrofolate
reductase so in
tetrafolate

Resistance

DHFR
reduce influx of
MTX

Clinical uses

AL,
NHL, cutaneous
lymphoma, Burkitts,
breast ca. Head and
neck ca.
Low- oral
Intermediate- im
High- iv

Admin
Pharmkinetics
sideefx

Extra notes

Myelosuppression,
rash
abortifacient

Leucovorin
replenishes folate

ANTIMETABOLITES against ca.

6- mercaptopurine
6- thioguanine (6- 5- flurouracil
(6-MP)
TG)
CCS (on S phase)
CCS (on S phase)
CCS (on S phase)
Uses HGPRT to
Analogue of
inhibit purine
pyrimidine
metabolism dysfx
interferes with
RNA and DNA results
conversion of
deoxyuridylic acid to
thymidylic acid
1. loose ablility to
convert the drug
to active form
2. thymidilate
synthetase
3. rate of drug
catbolism
ALL and CML
AML
Breast, ovarian
Colorectal, gastric

Cytarabine
CCS S phase)
Analogue of
pyrimidine
Inhibits DNA
polymerase
(which is S
phase)

AML
ALL
CNS leukemia

Iv
Metab in liver (first
pass)
hepatotoxicity

Fludarabine
(FAMP)
CCS (on S phase)
Analogue of
unnatural purine

Hairy cell
leukemia

iv
Urinary excretion

hepatotoxicity

Can combo with

daunorubicin and
cytarabine

BM depression
Ulcers in oral and GI
mucosa

Severe
myelosuppressio
n, ataxia,
dysarthria, dysdiadochokinesia
, cerebellar
disorders
*one of the most
active drugs in
leukemias

myelosuppresion

CCNS/CCS
Mech of action

Resistance
Clinical uses

Admin
Pharm-kinetics
sideefx
Extra notes

MICROTUBULE INHIBITORS against ca.

Vincristine (ONCOVIN)
Paclitaxel and Docetaxel
CCS
CCS that blocks mitosis in metaphase Freezes in polymerized state and
Prevents chrom segregation
stabilizes the microtub assembly
Therefore inhibits microtuble
formation
ALL in children, wilms, NHL
HL

Metab in liver
Neurotoxin: phlebitis or cellulitis
Part of MOPP for HL

Advanced endometrial caa.

Metastatic breast
Small cell lung
Squamous cell carcinoma
Head and neck
Iv
Metab in liver
Neutropenia
Premedicate with dexamethasone (a
corticosteroid)

Etoposide (VP16) , Teniposide (VM-26)

Binds to topoisomerase II
Works on G2 phase

Prostate
Testicular ca.
Small cell lung

Podophyllin alkaloids

Adrenocorticosteroid
s: prednisone,
dexamethasone
What is it?
Mech of action

Resistance
Clinical uses

Admin
Pharm-kinetics
sideefx
Extra notes

STEROID HORMONES against ca.

Tamoxifen
Estrogen

Leuprolide and
gosereline

Flutamide

nonapeptide

Nonsteroidal
antiandrogen

Block
production of
LH and syn
of androgens
in testes

LHRH agonists onto the

LHRH receptor of
pituitary inhibit LH
and FSH

Androgen
receptor
antagonist

Prostate ca.

Leuprolide: prostate ca.

Prostate ca.

Steroid, SERM: selective

esterogen receptive
modulator
Prednisone reduced by
dehydrogenase,
steroid binds to
receptor which is for
specific proteins
ALL
HL, NHL

Adjuvant trt and for trrt of

metastatic dz
Breast ca. And endometrail
ca.
*has the potential to cause
endometrial ca.
Mostly a antagonist and a
partial agonist for E
receptors must have the
receptor otwise doesnt work

Cisplatin and Carboplatin

What is it?
Mech of action

Cisplatin is a platinol
Carboplatin is a paraplatinol..
Both alkylaing agents
Alkylate agents, bind to DNA

MICELLANEOUS drugs against ca.

Procarbazi L-Asparaginase
ne
Another
An enzyme (from
alkylating
bacteria)
agent
Inhibit
Deaminates
DNA/RNA asparagine
syn
aspartic acid ca.
Needs asparagine and
takes it out of the pool
of nutrition
starvation
ALL

Clinical uses

Solid tumors:
testicular ca., ovarian ca

sideefx

Vomiting after 1 hr
Kidney dysfx

BM
depression

Extra notes

Extremely toxic
Testicular ca. also use combo of
vinblastine and bleomycin
Ovarian use with cyclophosphmide
Need to really hyrdrate the pt.
Use corticosteroids and antiserotonin
receptor against vomiting

Part of
MOPP
regimen for
HL

What is MOP???
What is COP or CHOP?
What is used for testicular ca?
What is used for breast ca.?

IFN-

Trastuzumab:
herceptin
Ab against HER2
protein

Unknown but
Leukocytic

Ab
ADCC via NK
and monocytes

Hairy cell leukemia

Squamous cell
carcinoma
Melanoma
MM

Breast ca.

Good efx: low BM

suppression and GI
suppression
Bad efx:
hypersensitivity
Can use in combo with
vincristine and
prednisone

Used in HL: mechlorethanimine, ONCOVIN, procarbazine, prednisone now replaced by ABVD

Used in NHL: cyclophosphamide, onceovin, prednisone, sometimes doxorubicin
PVB platinol (hydration), vinblastine, bleomycin (cisplastin is replacedby etoposide sometimes)
CMF cyclophosphamide, MTX, fleorouracil sometimes tamoxifen