• Clinical science

Chemotherapeutic agents

Abstract

Chemotherapeutic agents, also referred to as antineoplastic agents, are used to directly or indirectly inhibit the proliferation of rapidly growing cells, typically in the context of malignancy. They are classified according to their mechanism of action and include alkylating agents, antimetabolites, topoisomerase inhibitors, and mitotic inhibitors. Chemotherapy is associated with a range of adverse effects (e.g., nausea, vomiting, increased risk of infection, and impaired growth of healthy cells), and with some agents, an increased risk of secondary neoplasms. Symptomatic management of associated side effects is recommended to improve tolerance.

Overview

Chemotherapeutic agents
Drug class Subgroup Drug Indications

Alkylating agents

Topoisomerase inhibitors

Mitotic inhibitors

Antimetabolites

Other

  • Palliative chemotherapy of various tumors
  • Intravesical application following transurethral resection of urinary bladder carcinoma
  • Enzymes
  • Bortezomib
  • CML
  • GI stromal tumors

References:[1]

Effects

Drug class Subgroup Mode of action

Alkylating agents

  • Cross-links between DNA strandsDNA replication

Topoisomerase inhibitors

  • Topoisomerase II inhibitors
  • Inhibition of topoisomerase IIDNA degradation (ds-DNA breaks) and DNA replication

Mitotic inhibitors

Antimetabolites

  • Ribonucleotide reductase inhibitor

Antibiotics

Other

  • Enzymes
  • Prevents phosphorylation and activation of multiple proteins by tyrosine kinases → cell dysfunction and death

References:[1]

Side effects

General side effects

Chemotherapeutic agents damage rapidly growing tissues, but can also be neurotoxic and lead to peripheral neuropathy.

Side effects and characteristics of selected chemotherapeutic agents

Drug class Subgroup Side effects
Alkylating agents
  • Emetogenic
  • Myelotoxic
  • Emetogenic
  • Nephrotoxic (prevent with amifostine )
  • Ototoxic
  • Neurotoxic (central and peripheral neuropathies)
Topoisomerase inhibitors
  • Mainly myelotoxic (dose-limiting for topotecan)
  • Topoisomerase II inhibitors
  • Myelotoxic
Mitotic inhibitors
Antimetabolites
  • Myelotoxic
  • Hepatotoxic
  • Mucositis
  • Counter measure: “leucovorin (folinic acid) rescue”
  • Myelosuppression, nephrotoxicity, and neurotoxicity
  • Ribonucleotide reductase inhibitor
Other
  • Enzymes

References:[1][2]

We list the most important adverse effects. The selection is not exhaustive.

Indications

General indications

  • Neoadjuvant cytostatic therapy: : administered preoperatively to reduce tumor mass
  • Adjuvant cytostatic therapy: : administered postoperatively to reduce risk of recurrence and/or to improve prognosis
  • Palliative cytostatic therapy: : administered if curative therapy is not possible; ; indications vary (e.g., reduction of tumor-dependent symptoms)
  • Cytoreductive conditioning: high-dose cytostatic therapy; (sometimes in combination with whole body radiation) to suppress bone marrow before bone marrow or stem cell transplantation.

For specific indications see table under “Overview” above.

Guidelines & therapy recommendations

Oral administration of chemotherapy

Oral administration of cytostatic drugs allows for outpatient treatment and avoids the need for inpatient hospitalization (e.g., for patients in need of palliative chemotherapy).

Supportive therapy for radiochemotherapy

References:[3]

  • 1. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education; 2017.
  • 2. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education; 2014.
  • 3. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
last updated 11/08/2018
{{uncollapseSections(['M8bMMv', 'L8bwMv', 'o8b0nv', 'K8bUnv', '68bjnv', 'r8bfLv'])}}