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Chemotherapeutic agents

Last updated: July 10, 2021

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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). A consistent approach to the symptomatic treatment of adverse effects can considerably improve tolerance and, consequently, outcome.

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

Mitotic inhibitors

  • Nonspecific
  • Nonspecific
  • Nonspecific
Protein kinase inhibitors
  • Variable


  • Enzymes
  • PARP inhibitors
Monoclonal antibodies

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.

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.

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

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.

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.

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

ALK tyrosine kinase inhibitors

  • Alectinib
  • Crizotinib
  • GI toxicity (e.g., diarrhea)
  • Fluid retention and edema
  • Dermatologic toxicity (e.g., rash)
  • Ocular toxicity
  • Neurotoxicity
  • Hepatotoxicity
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
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.

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

Supportive therapy during chemotherapy

Supportive treatment during chemotherapy aims to prevent, limit, and treat complications of the underlying disease and the antineoplastic treatment.

General supportive measures

  • Infection prophylaxis (e.g., regular disinfection, protective gear, dental hygiene, avoidance of invasive measures)
  • Psychological support
  • Physiotherapy
  • Occupational therapy

Pharmaceutical therapy

Treatment of CINV [9][10][11][12][13]

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  12. Ifosfamide. Updated: January 1, 2020. Accessed: September 8, 2020.
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