Classification of Anticancer Drugs from Lippincott's Pharmacology

1. Alkylating Agents:

 Mechanism of Action (MOA): Alkylating agents work by forming covalent bonds with
DNA, leading to cross-linking of DNA strands, abnormal base pairing, or DNA strand
breakage. These disruptions interfere with DNA replication and transcription, ultimately
causing cell death.
 Use: They are effective against a variety of cancers including Hodgkin's disease, non-
Hodgkin's lymphoma, chronic lymphocytic leukemia (CLL), and multiple myeloma.
 Adverse Effects: Common side effects include myelosuppression (decreased production
of blood cells), nausea, vomiting, alopecia (hair loss), sterility, and an increased risk of
secondary malignancies due to the DNA damage they cause.
 Pharmacokinetics: Most alkylating agents are metabolized in the liver and excreted in
urine. They vary in their half-lives and tissue distribution, with some requiring activation
in the liver.
 Examples and Metabolites:
o Cyclophosphamide: Metabolized to active forms, including phosphoramide
mustard and acrolein.
o Ifosfamide: Metabolized to ifosfamide mustard and acrolein.
o Melphalan: No active metabolites.
o Chlorambucil: Metabolized to phenylacetic acid mustard.

2. Antimetabolites:

 Mechanism of Action (MOA): Antimetabolites mimic the normal substrates of essential

enzymatic reactions, thereby interfering with DNA and RNA synthesis. They inhibit the
enzymes involved in nucleotide synthesis or are incorporated into DNA or RNA,
disrupting their function.
 Use: These drugs are commonly used in the treatment of leukemias, lymphomas, and
cancers of the breast, ovary, and gastrointestinal tract.
 Adverse Effects: Side effects include myelosuppression, mucositis (inflammation of the
mucous membranes), diarrhea, and hand-foot syndrome (painful swelling and redness of
the hands and feet).
 Pharmacokinetics: Generally, antimetabolites are rapidly cleared from the plasma and
have variable oral bioavailability. They are metabolized in the liver and excreted via
urine.
 Examples and Metabolites:
o Folate Antagonists:
 Methotrexate: Polyglutamated inside cells to active forms.
o Purine Analogs:
 Mercaptopurine: Metabolized to 6-thioguanine nucleotides.
 Thioguanine: Metabolized to 6-thioguanine nucleotides.
o Pyrimidine Analogs:
 Fluorouracil (5-FU): Metabolized to 5-fluorodeoxyuridine
monophosphate (FdUMP).
  Cytarabine: Metabolized to ara-CTP.

3. Natural Products:

 Vinca Alkaloids:
o Mechanism of Action (MOA): Vinca alkaloids bind to tubulin and inhibit
microtubule formation, arresting cell division at metaphase.
o Use: They are used in the treatment of leukemia, lymphomas, and solid tumors
such as breast and lung cancer.
o Adverse Effects: Neurotoxicity (nerve damage), myelosuppression, and alopecia.
o Pharmacokinetics: These drugs are metabolized in the liver and excreted in bile.
o Examples and Metabolites:
 Vincristine: Metabolized to inactive metabolites.
 Vinblastine: Metabolized to inactive metabolites.
 Taxanes:
o Mechanism of Action (MOA): Taxanes promote microtubule assembly and
prevent their disassembly, leading to mitotic arrest and cell death.
o Use: Effective against breast cancer, ovarian cancer, and non-small cell lung
cancer.
o Adverse Effects: Myelosuppression, neuropathy (nerve damage), and
hypersensitivity reactions.
o Pharmacokinetics: Metabolized in the liver and excreted in bile.
o Examples and Metabolites:
 Paclitaxel: Metabolized to inactive metabolites.
 Docetaxel: Metabolized to inactive metabolites.
 Epipodophyllotoxins:
o Mechanism of Action (MOA): These drugs inhibit topoisomerase II, leading to
DNA strand breakage and cell death.
o Use: Used for testicular cancer, small cell lung cancer, and lymphomas.
o Adverse Effects: Myelosuppression, alopecia, nausea, and vomiting.
o Pharmacokinetics: Metabolized in the liver and excreted in urine.
o Examples and Metabolites:
 Etoposide: Metabolized to inactive metabolites.
 Teniposide: Metabolized to inactive metabolites.

4. Antibiotics:

 Mechanism of Action (MOA): Anticancer antibiotics intercalate with DNA, interfering

with DNA-dependent RNA synthesis and generating free radicals that cause DNA strand
breaks.
 Use: These drugs are widely used for various cancers including breast cancer, ovarian
cancer, and lymphomas.
 Adverse Effects: Myelosuppression, cardiotoxicity (heart damage), mucositis, and
alopecia.
 Pharmacokinetics: Metabolized in the liver, with excretion via bile and urine.
 Examples and Metabolites:
 o Doxorubicin: Metabolized to doxorubicinol.
o Daunorubicin: Metabolized to daunorubicinol.
o Bleomycin: Inactivated by bleomycin hydrolase.

5. Hormonal Agents:

 Mechanism of Action (MOA): These drugs modulate hormone receptors or inhibit the
synthesis of hormones that certain cancers depend on for growth.
 Use: Primarily used in breast cancer, prostate cancer, and endometrial cancer.
 Adverse Effects: Hot flashes, gynecomastia (breast enlargement in men),
thromboembolic events (blood clots), and osteoporosis.
 Pharmacokinetics: Variable based on the specific drug, often metabolized in the liver.
 Examples and Metabolites:
o Selective Estrogen Receptor Modulators (SERMs):
 Tamoxifen: Metabolized to endoxifen and 4-hydroxytamoxifen.
o Aromatase Inhibitors:
 Anastrozole: Metabolized to inactive metabolites.
 Letrozole: Metabolized to inactive metabolites.
o Antiandrogens:
 Flutamide: Metabolized to hydroxyflutamide.
 Bicalutamide: Metabolized to inactive metabolites.

6. Monoclonal Antibodies:

 Mechanism of Action (MOA): Monoclonal antibodies specifically target cancer cell

antigens, inducing an immune response against the cancer cells or delivering cytotoxic
agents directly to the cancer.
 Use: Used for various cancers including breast cancer, non-Hodgkin's lymphoma, and
colorectal cancer.
 Adverse Effects: Infusion reactions, myelosuppression, and cardiotoxicity.
 Pharmacokinetics: Long half-life, typically administered intravenously.
 Examples and Metabolites:
o Trastuzumab: No significant metabolites.
o Rituximab: No significant metabolites.
o Bevacizumab: No significant metabolites.

7. Tyrosine Kinase Inhibitors:

 Mechanism of Action (MOA): These drugs inhibit tyrosine kinases, which are enzymes
involved in the signaling pathways that regulate cell division and survival.
 Use: Effective for chronic myeloid leukemia (CML), gastrointestinal stromal tumors
(GIST), and non-small cell lung cancer.
 Adverse Effects: Diarrhea, rash, and hepatotoxicity (liver damage).
 Pharmacokinetics: Administered orally, metabolized in the liver, and excreted in feces.
 Examples and Metabolites:
o Imatinib: Metabolized to N-desmethyl imatinib.
 o Erlotinib: Metabolized to inactive metabolites.
o Gefitinib: Metabolized to inactive metabolites.

This comprehensive classification covers the primary groups of anticancer drugs, detailing their
mechanisms of action, uses, adverse effects, pharmacokinetics, and notable metabolites.

Steroid Hormones and Their Antagonists in Anticancer Therapy (Lippincott's

Pharmacology)

1. Selective Estrogen Receptor Modulators (SERMs)

 Tamoxifen
o MOA: Binds to estrogen receptors, blocking estrogen's proliferative action on breast
cancer cells.
o Use: Estrogen receptor-positive breast cancer.
o Adverse Effects: Hot flashes, increased risk of thromboembolic events, and endometrial
cancer.
o Pharmacokinetics: Metabolized in the liver to active metabolites (endoxifen, 4-
hydroxytamoxifen).

2. Aromatase Inhibitors

 Anastrozole, Letrozole
o MOA: Inhibit aromatase, reducing estrogen synthesis.
o Use: Postmenopausal women with estrogen receptor-positive breast cancer.
o Adverse Effects: Hot flashes, arthralgia (joint pain), and osteoporosis.
o Pharmacokinetics: Metabolized to inactive metabolites.

3. Antiandrogens

 Flutamide, Bicalutamide
o MOA: Bind to androgen receptors, blocking androgen effects.
o Use: Prostate cancer.
o Adverse Effects: Gynecomastia, liver toxicity, and hot flashes.
o Pharmacokinetics: Metabolized in the liver (flutamide to hydroxyflutamide).

4. GnRH (Gonadotropin-Releasing Hormone) Agonists

 Leuprolide, Goserelin
o MOA: Initially stimulate, then downregulate GnRH receptors, decreasing LH and FSH,
leading to reduced estrogen and testosterone.
o Use: Prostate cancer, breast cancer.
o Adverse Effects: Hot flashes, decreased libido, and osteoporosis.
o Pharmacokinetics: Administered via depot injection, metabolized to inactive peptides.
5. Glucocorticoids

 Prednisone, Dexamethasone
o MOA: Bind to glucocorticoid receptors, modulating gene expression to inhibit
lymphocyte proliferation.
o Use: Leukemias, lymphomas, and as supportive therapy to reduce inflammation and
immune response.
o Adverse Effects: Immunosuppression, hyperglycemia, and osteoporosis.
o Pharmacokinetics: Metabolized in the liver, with active and inactive metabolites
excreted in urine.