Cytotoxic antibiotics

Several naturally occurring compounds with antibiotic activity also have potent antitumour activity and were developed as anticancer agents. These cytotoxic antibiotics are often grouped together, even though they have diverse mechanisms of action, very different indications, a range of efficacies and distinctive toxicities.¹

Members

Bleomycin, daunorubicin, doxorubicin, dactinomycin, epirubicin, idarubicin, mitoxantrone and mitomycin.²

Method of action

Direct toxic action on cellular DNA.³

Indications include¹

• Bleomycin: used as an anticancer agent in the therapy of testicular and germ cell cancers, Hodgkin's disease, non-Hodgkin's lymphomas and tumours of the head and neck.

• Daunorubicin: an anthracycline antibiotic that is used in the therapy of acute leukaemia and AIDS related Kaposi's sarcoma.

• Doxorubicin, epirubicin and idarubicin are structurally related cytotoxic antineoplastic antibiotics used in the therapy of several forms of lymphoma, leukaemia, sarcoma and solid organ cancers, including ovarian cancer.⁴

• Dactinomycin: an intravenously administered, antineoplastic antibiotic that is used in the treatment of solid tumours in children and choriocarcinoma in adult women.

• Mitoxantrone: an antineoplastic antibiotic that is used in the treatment of acute leukaemia, lymphoma, and prostate cancer and breast cancer.

• Mitomycin: a cytotoxic antibiotic which is used as anticancer therapy of advanced cancers of the stomach and pancreas.

Important interactions and cautions

The interactions and cautions are variable for each of the cytotoxic antibiotics. The following is a very brief summary. Cytotoxic antibiotics are used in treatments provided in secondary and tertiary care. Always seek specialist advice if there are any concerns about a patient that may be attributable to their treatment.

• Radiotherapy - some cytotoxic antibiotics can result in toxicity.

• Irreversible cardiotoxicity - must be used cautiously in patients with previous cardiac illness.⁵ (A liposomal formulation of doxorubicin is available which is associated with less cardiotoxicity.)

• Liver impairment.

• Skin reactions - especially with doxorubicin.

Adverse effects

The adverse effects are variable for each of the cytotoxic antibiotics. The following is a very brief summary.

• Myelosuppression - usually occurs at 2-4 weeks with complete recovery by eight weeks. Rare with bleomycin, whereas mitomycin is associated with delayed myelosuppression.

• Extravasation causes severe skin necrosis.

• Excreted in bile; therefore, it is necessary to monitor bilirubin levels - if high, dose reduction is needed.

• Associated with cardiac toxicity - this is rare and includes supraventricular tachycardia (SVT) and cardiomyopathies (related to dose).