Mechanism of action:

Inhibit the replication of DNA.

  1. Cytidine analogs
Name Structure
Azacytidine azacytidine
Decitabine decitabine
Cytarabine cytarabine
Gemcitabine gemcitabine

MoA: Directly incorporate into DNA and inhibit DNA methyltransferase (azacitidine, decitabine) or DNA polymerase (cytarabine, gemcitabine)

  • Indications: Azacitidine and decitabine for MDS, AML, cytarabine for MDS, AML, and gemcitabine for breast, NSCLC, ovarian, pancreatic, bladder, sarcoma, Hodkin lymphoma, NHL
  • Toxicity: Myelosuppression in general. Cytarabine high dose causes neurotoxicity, conjunctivitis. Gemcitabine causes liver enzyme elevations, interstitial pneumonitis.
  1. Folate antagonists
Name Structure
Methotrexate methotrexate
Pemetrexed pemetrexed

MOA: Reduces folate, which is essential in the synthesis of purine nucleotides and thymidylate

  • Indications: Methotrexate for ALL, NHL, CNS, sarcoma, and pemetrexed for malignant pleural mesothelioma, NSCLC (non-squamous)
  • Toxicity: Myelosuppression, mucositis, hepatotoxicity, nephrotoxicity, cutaneous reactions
  • Toxicity prevention: Hydration and alkalization of the urine, leucovorin rescue
  1. Purine analogs
Name Structure
Cladribine cladribine
Clofarabine clofarabine
Nelarabine nelarabine

MOA: structural analogs of guanine and act as false metabolites

  • Indications: Cladribine for hairy cell leukemia, AML, CLL, NHL. Clofarabine for ALL, AML. fludarabine for CLL, AML, NHL, BMT conditioning agent. Nelarabine for T-ALL, lymphoma. Pentostatin for hairy cell leukemia, CTCL, CLL.
  • Toxicities: Myelosuppression, immunosuppression (suppress CD4+ cells) put patients at risk for opportunistic infections
  1. Pyrimidine analogs
Name Structure
Fluorouracil (5-FU) fluorouracil
Capecitabine (prodrug of 5-FU) capecitabine

MOA: Active metabolite (F-dUMP) forms a stable covalent complex with thymidine synthetase in the presence of reduced folate, therefore, interfering with DNA synthesis and repair.