Anthracyclines
Doxorubicin (Streptomyces peucetius)
Daunorubicin
Indications
Carcinoma, sarcoma. Not Ca renal cell, bronchogenic, colonic.
Mechanism
Intercalate DNA, binds iron → generates free radicals,
peroxidises lipids.
Does not cross blood-brain barrier, so will not touch CNS mets.
Adverse effects
Aesthenia, palmar-plantar erythrodysaesthesia,
myelosuppression (anaemia, neutropaenia,
thrombocytopaenia), mucositis, alopecia.
Risk of dilated cardiomyopathy at high doses, Dexrazoxane
used concommitantly as cardioprotective (not licensed in UK).
Points of interest
Available in liposomal form. MPEG on the surface protects
the liposomes from opsonisation by plasma proteins and subsequent
detection as a foreign molecule by the mononuclear
phagocyte system.