Antibiotic cytotoxics typically were developed as antibiotic agents but found to be highly toxic to human cells as well as bacteria. This makes them useful in some malignancies.
Actinomycin D (aka dactinomycin)
This is an older chemotherapy agent and has been in use since the 1970s.
Mechanism of Action
Actinomycin D binds to the DNA of cells; it thereby prevents RNA transcription and is therefore cytotoxic.
Pancytopaenia, hair loss, mouth ulcers, liver toxicity. It can cause second malignancies.
Use with radiotherapy
Treatment with actinomycin D can cause reactivation of radiation toxicity, often of the skin. It is typically avoided for concurrent radiotherapy.
Actinomycin D is used in a number of paediatric malignancies (rhabdomyosarcoma, Wilms tumour, Ewing sarcoma) and occasionally germ cell tumours.
The anthracyclines are commonly used antibiotic cytotoxics, and include epirubicin and doxorubicin.
Mechanism of Action
Anthracyclines have multiple mechanisms of action within cells. They impair the function of topoisomerase II which also leads to cell death as well as allowing them to be caelate into the DNA molecule. They impair DNA helicase which prevents RNA transcription due to inability to unwind the DNA helix. Finally, they also create free radicals which may cause further DNA damage.
Anthracyclines are potent emetic agents. They also cause pancytopaenia and alopecia. Late effects on the heart are due to myocyte damage, leading to left ventricular impairment and heart failure. This is in contrast to radiotherapy effects on the heart, which cause fibrosis (restrictive changes) and impair vascular supply. Combination of these two effects can cause significant long term cardiomyopathies.
Interaction with Radiotherapy
Anthracyclines are potent sensitisers for radiotherapy and can even cause radiation recall if used after radiotherapy has been previously delivered. AVOID.
Anthracyclines are used widely as systemic therapy. They are perhaps best known for breast cancer treatment.