Antitumor Antibiotics

Dactinomycin (Actinomycin D)

• Mechanism 
  • intercalate between strands of DNA
• Clinical use
  • Wilms’ tumor
  • Ewing’s sarcoma
  • rhabdomyosarcoma
  • childhood tumors
• Toxicity
• myelosuppression

Doxorubicin (Adriamycin) and Daunorubicin

• Mechanism 
  • intercalate between strands of DNA
    • noncovalent
    • breaks DNA → decreased replication
  • free radical generation
  • inhibit topoisomerase
• Clinical use
  • Hodgkin’s lymphomas
    • part of the ABVD combination regimen
      • Adriamycin
      • Bleomycin
      • Vinblastine
      • Dacarbazine
  • solid tumors
    • breast, endometrial, ovary, and lung
  • myelomas
  • sarcomas
• Toxicity
  • cardiotoxicity
    • dilated cardiomyopathy
    • dexrazoxane used to prevent cardiotoxicity
      • iron chelating agent
      • prevents formation of free radicals
        • does not “trap” free radicals
  • myelosuppression
  • alopecia
• tissue damage if extravasates into extravascular space

Bleomycin

• Mechanism
  • free radical generation
    • complexes with Fe and O₂
    • breaks DNA → decreased replication
  • G₂-phase specific
• Clinical use
  • Hodgkin’s lymphoma
    • part of ABVD regimen for Hodgkin’s
  • testicular cancer
  • head and neck cancer
  • skin cancer
• Toxicity
  • pulmonary fibrosis 
  • pneumonitis
  • skin changes
• myelosuppression is relatively insignificant

Etoposide (VP-16) and Teniposide

• Mechanism
  • inhibits DNA topoisomerase II (think eTWOposide)
    • breaks DNA → decreased replication
  • late S- to G₂-phase specific
• Clinical use
  • small cell carcinoma
    • lung
    • prostate
  • testicular carcinoma
• Toxicity
  • myelosuppression
  • GI upset
• alopecia

Irinotecan and Topotecan

• Mechanism
  • inhibits DNA topoisomerase I (think 1rinotecan)
    • prevents DNA replication by inhibiting DNA unwinding
• Clinical use
  • colon, ovarian, and small cell lung cancer
• Toxicity
  • myelosuppression
  • diarrhea