Chemotherapeutic agents

Last updated: August 28, 2023

Summarytoggle arrow icon

Chemotherapeutic agents, also referred to as antineoplastic agents, are used to directly or indirectly inhibit the uncontrolled growth and proliferation of cancer cells. They are classified according to their mechanism of action and include alkylating agents, antimetabolites, topoisomerase inhibitors, antibiotics, mitotic inhibitors, and protein kinase inhibitors. Chemotherapy is associated with a range of adverse effects (e.g., nausea, vomiting, immunosuppression, and impaired growth of healthy cells), and some agents increase the risk of secondary neoplasm development. For some chemotherapeutic agents, specific detoxifying agents can be administered to avert preventable side effects (e.g., leucovorin after application of methotrexate, mesna after cyclophosphamide application).

For further information of management chemotherapy-related complications, see “Principles of cancer care.”

Overviewtoggle arrow icon

Basics of chemotherapeutic agents action [1][2]

  • Kinetics
    • Chemotherapeutic agents are most active on cells with a high growth fraction, i.e., cells actively undergoing division (including normal cells, such as epithelial or bone marrow cells, as well as cancer cells)
    • The log-kill hypothesis is a mathematical model of chemotherapeutic agent action, according to which a given dose of a certain chemotherapeutic agent eliminates a constant fraction of cancer cells regardless of tumor size. [3]
  • Cell cycle specificity
    • Cell cycle-specific antineoplastic agents act on proliferating cells only during a specific phase of the cell cycle. There is no cell-cycle specific antineoplastic agent that acts during the resting (G0) phase.
    • Cell cycle-nonspecific antineoplastic agents act on cells at any phase of the cell cycle, including the resting (G0) phase.
  • Resistance mechanisms: cancer cells can develop resistance to chemotherapeutic agents via the following mechanisms

Basics of chemotherapy

For more information, see “Antineoplastic therapy” in “General oncology.”

Combination therapy

Chemotherapeutic agents are usually used in combination (combined chemotherapy regimens).

Routes of administration

The most common route of administration for chemotherapy is intravenous; other important methods of delivery include oral, intrathecal, and topical application.

Efficacy of treatment

Common adverse effects of chemotherapy

Chemotherapeutic agents damage actively dividing cells, but can also affect tissues with a low mitotic potential (e.g., neurons).

Gastrointestinal tract




Sexual organs

Overview of chemotherapeutic drugs classes

Overview of important chemotherapeutic agents
Drug class Subgroup Drug

Cell cycle specificity



  • Nonspecific

Alkylating agents

  • Nonspecific

Topoisomerase inhibitors

  • Teniposide

Mitotic inhibitors

  • Nonspecific
  • Nonspecific
  • Nonspecific
Protein kinase inhibitors (e.g., tyrosine kinase inhibitors)
  • Variable


  • Enzymes
  • PARP inhibitors
Monoclonal antibodies

Antimetabolitestoggle arrow icon

Overview of important antimetabolites
Subgroup Agent Mechanism of action Indications Adverse effects


  • Methotrexate
  • Pemetrexed
  • Multitargeted antifolate
  • Inhibition of thymidylate synthase ↓ synthesis of deoxythymidine monophosphate (dTMP) → DNA and RNA synthesis

Pyrimidine antagonists

  • Cytarabine
  • 5-Fluorouracil (5-FU)
  • Capecitabine (prodrug for 5-FU)
  • Gemcitabine

Purine antagonists

  • Fludarabine
  • Cladribine

Ribonucleotide reductase inhibitors

Cytarabine causes myelosuppression with pancytopenia.

Alkylating agentstoggle arrow icon

Overview of important alkylating agents
Subgroup Agent Mechanism of action Indications

Adverse effects


  • Cyclophosphamide
  • Ifosfamide

Nitrogen mustards

  • Chlorambucil
  • Melphalan


  • Temozolomide


  • Carmustine
  • Lomustine
  • Streptozocin

Alkyl sulfonate

  • Busulfan


  • Procarbazine
Platinum-based agents
  • Cisplatin
  • Carboplatin
  • Oxaliplatin

Cyclophosphamide can cause hemorrhagic cystitis.

Busulfan and Bleomycin Block your Breath: busulfan and bleomycin cause pulmonary fibrosis.

Topoisomerase inhibitorstoggle arrow icon

Overview of important topoisomerase inhibitors
Subgroup Agent Mechanism of action Indications Adverse effects

Topoisomerase I inhibitors

  • Irinotecan
  • Inhibition of topoisomerase I DNA unwinding → DNA replication and DNA degradation (because of ssDNA breaks)
  • Topotecan

Topoisomerase II inhibitors

  • Etoposide

Mitotic inhibitorstoggle arrow icon

Overview of important mitotic inhibitors

Subgroup Agent Mechanism of action Indications Adverse effects

Vinca alkaloids

  • Vincristine
  • Vinblastine
  • Myelosuppression
  • Extravasation can cause significant irritation of local tissue
  • Pulmonary toxicity
  • Vinorelbine


  • Docetaxel
  • Paclitaxel
Nontaxane microtubule inhibitors
  • Eribulin
  • Ixabepilone
  • Epothilone

The tax rates are stable: taxanes stabilize microtubules.

Assemblies are not permitted in the vineyard: vinca alkaloids prevent microtubule assembly.

Vincristine crisps the nerves and vinblastine blasts the bone marrow.

Antitumor antibioticstoggle arrow icon

Overview of important cytotoxic antibiotics
Agent Mechanism of action Indications Side effects


Actinomycin D (dactinomycin)


(doxorubicin, daunorubicin, idarubicin)

  • Inhibition of topoisomerase II DNA degradation (dsDNA breaks) and DNA replication
  • Formation of free radicals breakage of DNA strands
  • DNA intercalation breakage of DNA strands and DNA replication
  • Cross-linking between DNA strands → DNA and RNA synthesis

Busulfan and bleomycin block your breath: Busulfan and bleomycin cause pulmonary fibrosis.

Except for bleomycin, all antitumor antibiotics are cell cycle nonspecific agents. Bleomycin is effective against cells in the G2 and M phase.

Protein kinase inhibitorstoggle arrow icon

Overview of important protein kinase inhibitors
Subgroup Agent Mechanism of action Indications Side effects

BCR-ABL and c-KIT tyrosine kinase inhibitors

  • Imatinib
  • Dasatinib
  • Nilotinib
EGFR tyrosine kinase inhibitors
  • Erlotinib
  • Gefitinib
  • Afatinib
  • Osimertinib
VEGFR tyrosine kinase inhibitors [10][11]
  • Inhibition of VEGF tyrosine kinase multimodal change to tumor microenvironment via antiangiogenic effect, effects on vessel function, and immune modulation [12]

ALK tyrosine kinase inhibitors

  • Alectinib
  • Crizotinib
V600E mutated-BRAF oncogene inhibitors
  • Dabrafenib
  • Encorafenib
  • Vemurafenib
MEK inhibitors
  • Trametinib
  • Inhibition of MAP kinase signaling pathway → inhibition of cancer cell growth and induction of apoptosis
Bruton kinase inhibitors
  • Ibrutinib
Janus kinase inhibitors
  • Ruxolitinib
CDK inhibitors
  • Palbociclib

Otherstoggle arrow icon

Overview of chemotherapeutic agents from other groups
Subgroup Agent Mechanism of action Indications Side effects


  • L-asparaginase

Proteasome inhibitors

  • Bortezomib
  • Carfilzomib
  • Ixazomib
PARP Inhibitors
  • Olaparib
  • Inhibition of poly (ADP-ribose) polymerase → ↓ repair of single-strand DNA breaks
Monoclonal antibodies

VemuRAFenib and daBRAFenib are BRAF inhibitors.

Additional considerationstoggle arrow icon

Detoxifying agents for antineoplastic treatment

The toxicity of certain chemotherapeutic agents can be prevented by the administration of particular detoxifying agents.

Overview of important detoxifying agents for antineoplastic treatment
Subgroup Agent Preventable adverse effect Detoxifying agent
  • Mesna (2-MErcaptoethane Sulfonate Na) and fluids
  • The sulfate group of mesna binds toxic metabolites
Platinum-based agents
  • Cardiotoxicity

Management of complications

Referencestoggle arrow icon

  1. Zirlik K, Duyster J. Anti-Angiogenics: Current Situation and Future Perspectives. Oncol Res Treat. 2018; 41 (4): p.166-171.doi: 10.1159/000488087 . | Open in Read by QxMD
  2. Cohen RB, Oudard S. Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities. Invest New Drugs. 2012; 30 (5): p.2066-2079.doi: 10.1007/s10637-012-9796-8 . | Open in Read by QxMD
  3. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008; 8 (8): p.579-591.doi: 10.1038/nrc2403 . | Open in Read by QxMD
  4. CYCLOPHOSPHAMIDE. Updated: January 1, 2012. Accessed: September 8, 2020.
  5. Ifosfamide. Updated: January 1, 2020. Accessed: September 8, 2020.
  6. Armand J-P, Ribrag V, Harrousseau J-L, Abrey L. Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors. Therapeutics and Clinical Risk Management. 2007; 3 (2): p.213-224.doi: 10.2147/tcrm.2007.3.2.213 . | Open in Read by QxMD
  7. Brunton L. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition. McGraw-Hill Education / Medical ; 2017
  8. Cladribine. Updated: December 1, 2019. Accessed: September 9, 2020.
  9. Volkova M, Russell R. Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment. Current Cardiology Reviews. 2012; 7 (4): p.214-220.doi: 10.2174/157340311799960645 . | Open in Read by QxMD
  10. Trevor AJ, Katzung BG, Knuidering-Hall M. Katzung & Trevor's Pharmacology Examination and Board Review,11th Edition. McGraw Hill Professional ; 2015
  11. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014
  12. Traina TA, Norton L. Log-Kill Hypothesis. Springer Berlin Heidelberg ; 2017: p. 2074-2075
  13. Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: mechanisms of action and clinical strategies. Nature Reviews Cancer. 2003; 3 (5): p.330-338.doi: 10.1038/nrc1074 . | Open in Read by QxMD

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