Cladribine & Pentostatin

Summary

Cladribine and pentostatin are drugs used primarily to treat hairy cell leukemia. As antimetabolites, both drugs work as purine analogs to interfere with DNA synthesis and kill cancer cells.

Cladribine is unable to be processed by the enzyme ADA, so it instead accumulates inside the cell, where it can not only disrupt DNA synthesis but also directly impair metabolism. Cladribine is cell cycle non-specific, damaging cells across all phases of the cell cycle.

In contrast, pentostatin is a direct inhibitor of ADA but is thought to be less directly toxic to the cell. Pentostatin is S-phase specific.

Key Points

• Cladribine, Pentostatin
  • Drug Class
    • Antimetabolite
  • Mechanism
    • Purine analogs
      • Cladribine
        • Unable to be processed by ADA
          • Cladribine is resistant to degradation by ADA, allowing it to accumulate in cells. Its phosphorylated form is also incorporated into DNA, leading to strand breaks
        • Cladribine is cell-cycle nonspecific
          • Can also target resting (non-dividing) cells
      • Pentostatin
        • Directly inhibits ADA
          • Pentostatin directly inhibits ADA, causing accumulation of deoxyadenosine during DNA replication
        • Pentostatin is S-phase specific
    • Interferes with DNA synthesis
  • Clinical Use
    • Treat hairy cell leukemia
  • Side Effects
    • Myelosuppression