Classification of Anticancer Drugs (1)

Cancer is characterized by uncontrolled cell growth and the ability of malignant cells to invade other tissues. Anticancer drugs, also called antineoplastic agents, are used to destroy or inhibit the proliferation of cancer cells. These drugs work through a variety of mechanisms and are classified based on their mode of action and chemical structure.

This blog from Pharmacy Freak covers the classification, uses, drug of choice highlights, side effects, and clinical pearls relevant for academic and clinical understanding of anticancer pharmacology.

What is Anticancer Drug (1)

Anticancer drugs are pharmacological agents used in the treatment of malignant tumors. They act by interfering with cell division or damaging DNA, leading to the death of rapidly dividing cancer cells.

Classification of Anticancer Drugs (KD Tripathi)

ANTICANCER DRUGS (1) – Cytotoxic Drugs (1)

  • lkylating agents
    • Nitrogen mustards: Mechlorethamine, Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan
    • Ethylenimine: Thiotepa
    • Alkylsulfonate: Busulfan
    • Nitrosoureas: Carmustine, Lomustine
    • Triazine: Dacarbazine, Temozolomide
    • Methyl hydrazine: Procarbazine
  • Platinum coordination complexes
    Cisplatin, Carboplatin, Oxaliplatin
  • Antimetabolites
    • Folate antagonists: Methotrexate, Pemetrexed
    • Purine antagonists: 6-Mercaptopurine, 6-Thioguanine, Azathioprine, Fludarabine
    • Pyrimidine antagonists: 5-Fluorouracil, Capecitabine, Cytarabine

Classification of Anticancer Drugs (General)

Anticancer drugs are broadly classified into the following categories:

  1. Alkylating Agents
    Mechanism: Form covalent bonds with DNA, leading to cross-linking and inhibition of replication
    Examples: Cyclophosphamide, Ifosfamide, Chlorambucil, Busulfan, Melphalan
    Use: Broad spectrum – lymphomas, leukemias, breast and ovarian cancers
  2. Platinum Coordination Complexes
    Mechanism: Form DNA cross-links similar to alkylating agents
    Examples: Cisplatin, Carboplatin, Oxaliplatin
    Use: Testicular, ovarian, bladder, and colorectal cancers
  3. Antimetabolites
    Mechanism: Inhibit enzymes required for nucleotide synthesis
    Subtypes:
  • Folate antagonists: Methotrexate
  • Purine analogues: 6-Mercaptopurine, 6-Thioguanine
  • Pyrimidine analogues: 5-Fluorouracil, Cytarabine, Capecitabine
    Use: Leukemias, breast cancer, colorectal cancer
  1. Plant Alkaloids
    a. Vinca alkaloids
    Mechanism: Inhibit microtubule assembly
    Drugs: Vincristine, Vinblastine
    b. Taxanes
    Mechanism: Stabilize microtubules, preventing depolymerization
    Drugs: Paclitaxel, Docetaxel
    c. Epipodophyllotoxins
    Mechanism: Inhibit topoisomerase II
    Drugs: Etoposide, Teniposide
    d. Camptothecins
    Mechanism: Inhibit topoisomerase I
    Drugs: Topotecan, Irinotecan
    Use: Breast cancer, lung cancer, lymphomas, leukemias
  2. Antibiotics (Cytotoxic)
    Mechanism: Intercalate into DNA, inhibit topoisomerase II, generate free radicals
    Examples: Doxorubicin, Daunorubicin, Bleomycin, Mitomycin C
    Use: Leukemias, lymphomas, sarcomas, solid tumors
  3. Hormonal Agents
    a. Estrogen antagonists: Tamoxifen (breast cancer)
    b. Aromatase inhibitors: Letrozole, Anastrozole
    c. Androgen antagonists: Flutamide, Bicalutamide (prostate cancer)
    d. GnRH analogues: Leuprolide, Goserelin
    Use: Hormone-sensitive cancers
  4. Monoclonal Antibodies
    Mechanism: Target specific cell surface antigens
    Examples:
  • Rituximab (CD20 – B-cell lymphoma)
  • Trastuzumab (HER2 – breast cancer)
  • Cetuximab (EGFR – colorectal and head-neck cancer)
  1. Tyrosine Kinase Inhibitors
    Mechanism: Inhibit intracellular kinase pathways involved in tumor growth
    Examples:
  • Imatinib (BCR-ABL in CML)
  • Erlotinib, Gefitinib (EGFR)
  • Sunitinib, Sorafenib (VEGF receptors)
  1. Immunomodulators
    Examples: Interferons, Interleukins, Thalidomide
    Use: Melanoma, renal cell carcinoma, multiple myeloma
  2. Miscellaneous Agents
    Examples: Hydroxyurea, Asparaginase, Procarbazine
    Use: Chronic myelogenous leukemia, acute lymphoblastic leukemia, Hodgkin’s disease

Uses

Anticancer drugs are used for:

  • Curative therapy in hematological malignancies
  • Palliative therapy in advanced cancers
  • Adjuvant or neoadjuvant therapy in solid tumors
  • Prevention of recurrence or metastasis
  • Immunotherapy in specific cancers (melanoma, renal cell carcinoma)

Drug of Choice Highlights

  • Acute lymphoblastic leukemia – Vincristine + Prednisolone + Asparaginase
  • Chronic myeloid leukemia – Imatinib
  • Breast cancer – Tamoxifen (ER-positive), Trastuzumab (HER2-positive)
  • Prostate cancer – Leuprolide + Flutamide
  • Testicular cancer – Cisplatin + Etoposide + Bleomycin
  • Hodgkin’s lymphoma – ABVD regimen (Adriamycin, Bleomycin, Vinblastine, Dacarbazine)
  • Osteogenic sarcoma – Methotrexate + Doxorubicin + Cisplatin
  • Multiple myeloma – Bortezomib + Thalidomide + Dexamethasone

Side Effects

  • Alkylating agents – Bone marrow suppression, infertility, secondary malignancies
  • Platinum compounds – Nephrotoxicity, ototoxicity, peripheral neuropathy
  • Antimetabolites – Myelosuppression, mucositis, hepatotoxicity
  • Vinca alkaloids – Neurotoxicity (Vincristine), myelosuppression (Vinblastine)
  • Taxanes – Myelosuppression, hypersensitivity reactions
  • Anthracyclines – Cardiotoxicity (Doxorubicin)
  • Bleomycin – Pulmonary fibrosis
  • Hormonal agents – Hot flashes, thromboembolism, osteoporosis
  • Monoclonal antibodies – Infusion reactions, cardiotoxicity (Trastuzumab)
  • TKIs – Diarrhea, rash, hepatotoxicity, QT prolongation

Updated Clinical Pearls

  • Targeted therapies have improved survival in cancers like CML and breast cancer with fewer systemic toxicities.
  • Cardiotoxicity with anthracyclines is dose-dependent; cumulative dose monitoring is essential.
  • Supportive therapies like antiemetics, colony-stimulating factors, and hydration protocols reduce treatment-related complications.
  • Combination chemotherapy is often more effective due to synergistic mechanisms and reduced resistance.
  • Monitoring of renal, hepatic, and cardiac function is necessary throughout treatment.

References

  1. Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 829–846
  2. Gupta S, Garg A. Review of Pharmacology. 15th ed. New Delhi: Jaypee Brothers Medical Publishers; 2023. p. 275–277
  3. Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Education; 2011. p. 1667–1692

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