Antineoplastic Agents

ANTIBETABOLITES
Drug
Methotrexate (MTX)

Mechanism
Folic acid analog that inhibits
dihydrofolate reductase to decrease
dTMP and decrease DNA and Protein
synthesis

Clinical Use
Leukemia, lymphoma,
choriocarcinoma

5-fluorouracil (5-FU)

Pyrimidine analog bioactivated to 5FdUMP, which covalently complexes

folic acid.

Colon cancer and other solid tumors,

basal cell carcinoma, synery with
MTX

6-mercaptopurine (6-MP)

Purine analog to decrease purine

synthesis

Leukemias, lymphomas (not CLL or

Hodgkins)

6-thioguanine (6-TG)

Same as 6-MP

Acute Lymphoid leukemia

Cytarabine (ara-C)

Pyrimidine antagonist to decrease

DNA polymerase

AML, ALL, high grade non hodgkins

lymphoma

Mechanism
Intercalates in DNA

Clinical Use
Wilms tumor, Ewings sarcoma,
rhabdomyosarcoma
Hodgkins lymphomas; also for
myelomas, sarcomas, and solid
tumors

ANTIBIOTICS
Drug
Dactinomycin (Actinomycin D)
Doxorubicin (Adriamycin);
daunorubicin

Generate free radicals. Noncvalently

intercalate in DNA to breaks in DNA to
decrease replication

Bleomycin

Induces free radical formation, which

causes breaks in DNA strands

Testicular cancer, Hodgins lymphoma

Etoposide (VP-16); teniposide

Inhibits topoisomerase II increase

DNA degradation

Small cell carcinoma of the lung and

prostate, testicular carcinoma

Toxicity
l. Myelosuppression,
which is reversible
with leucovorin
(folinic acid) "rescue."
2. Macrovesicular fatty
change in liver.
3. Mucositis.
4. Teratogenic.
l. Myelosuppression,
which is not reversible
with leucovorin.
Overdose: "rescue"
with thymidine.
2. Photosensitivity
Bone marrow, GI,
liver. Metabolized
by xanthine oxidase;
thus I toxicity with
allopurinol.
Bone marrow depression,
liver.
Can be given with
allopurinol.
Leukopenia,
thrombocytopenia,
megaloblastic anemia.

Toxicity
Myelosuppression.
Cardiotoxicity,
myelosuppression, and
alopecia. Toxic to tissues
with extravasation.
Pulmonary fibrosis, skin
changes. Minimal
myelosuppression.
Myelosuppression, Gl
irritation, alopecia.

ALKYLATING AGENTS
Drug
Cyclophosphamide; ifosfamide

Nitrosureas (carmustine, lomustine,

semustine, streptozocin)
Busulfan

MICROTUBULE INHIBITORS
Drug
Vincristine; vinblastine

Paclitaxel

Mechanism
Covalently X link DNA at guanine N-7.
Require bioactivation by liver

Clinical Use
Non hodgkins lymphoma, breast and
ovarian carcinomas. Also
immunosuppressant

Toxicity

Require bioactivation. Cross blood

brain barrier to CNS
Alkylates DNA

Brain tumors (including glioblastoma

multiforme)
CML. Also used to ablate patients
bone marrow before bone marrow
transplantation

Mechanism
Alkaloids that bind to tubulin in Mphase and block polymerization of
microtubules so that mitotic spindle
cannot form. Microtubules are the
vines of your cells.

Clinical Use
Hodgkins lymphoma, Wilms tumor
choriocarcinoma

Toxicity
Vincristine- neurotoxicity (areflexia,
peripheral block polymerization
choriocarcinoma. neuritis), paralytic
ileus. VinBLASTine BLASTs Bone
marrow

Hyperstabilize polymerized
microtubules in M-phase so that
mitotic spindle cannot break down.
It is Taxing to stay polymerized.

Ovarian and breast carcinomas

Myelosuppression and
hypersensitivity.

Myelosuppression;
hemorrhagic cystitis,
partially prevented
with mesna (thiol
group of mesna binds
toxic metabolite).
CNS toxicity (dizziness,
ataxia).
Pulmonary fibrosis,
hyperpigmentation.