Classic alkylating agents interfere with DNA replication by crosslinking DNA strands, DNA strand breaking, and abnormal pairing of base pairs. They exert their lethal effects on cells throughout the cell cycle but tend to be more effective against rapidly dividing cells.1, 7, 11
Because alkylating agents are active against cells in G0, they can be used to debulk tumours, causing resting cells to be recruited into active division. At this point, those cells are vulnerable to the cell cycle-specific agents. These agents are active against lymphomas, Hodgkin's disease, breast cancer, and multiple myeloma.1, 7, 11
Major toxicities occur in the haematopoietic, gastrointestinal and reproductive systems. Individuals treated with these agents are also placed at a higher risk of developing secondary malignancies. Examples include Cyclophosphamide, Ifosfamide, Chlorambucil, Busulfan and Melphalan.1, 7, 11
The nitrosureas are a subgroup of the alkylating agents. They also interfere with DNA replication and repair. They are highly lipid soluble and readily cross the blood-brain barrier. An example is Carmustine.1, 7, 11
Another subgroup of alkylators called Platinum-containing compounds include agents such as Cisplatin, Carboplatin and Oxaliplatin.12 Their cytotoxic properties also extend to alteration of the cell membrane transport systems and suppression of mitochondrial function.
Choose an alkalyting agent and discuss its:
- Indications in cancer control.
- Mechanism of action.
- Adverse effects.
- Administration considerations.