The End of Cytotoxics?

European Oncology & Haematology, 2011;7(4):228-233


Cytotoxic drugs were the first form of cancer chemotherapy to be established, but they can have quite severe side effects. Cytotoxics attack all rapidly dividing cells, including healthy cells and cancer cells. They can therefore cause side effects such as loss of hair, damage to the skin and mucosa, and damage to bone marrow, affecting the immune system. For this reason, the focus of some cancer research has moved from cytotoxics to targeted therapeutics, including monoclonal antibodies. Monoclonal antibodies can be very effective in patients who express the appropriate target; however, not all patients do, and some develop resistance. Monoclonal antibodies, like other biologicals, are also very costly. All is not lost for cytotoxics. Because they have been around for so long, there is an abundance of data on their modes of action. Based on these data, researchers have developed newer cytotoxics that are more effective and have fewer side effects, and approaches that deliver cytotoxics more safely or target them to tumours.
Keywords: Antigens, cancer, cytotoxics, drug delivery, monoclonal antibodies, targeting
Disclosure: Nalân Utku is Managing Director of CellAct Pharma GmbH, a biotech company focused on the development of innovative therapeutics.
Received: May 05, 2011 Accepted September 06, 2011 Citation European Oncology & Haematology, 2011;7(4):228-233
Correspondence: Nalân Utku, Institut für Medizinische Immunologie, Charité Universitätsmedizin Berlin, Campus Virchow-Clinikum, Augustenburger Platz 1, 13353 Berlin, Germany. E:

Cancer is characterised by uncontrolled and unlimited multiplication of cells outpacing the natural rate of cell death (apoptosis).1 The treatment of cancer involves cytotoxic or targeted therapeutics that kill the cancer cells, stop their multiplication, inhibit metastasis or break tolerance against cancer cells by modulating T-regulatory cells or antigen-presenting/T-cell recognition via vaccination (see Figure 1).
According to the WHO, cancer is one of the leading causes of death worldwide. There were around 7.4 million deaths from cancer in 2004, predicted to rise to around 12 million in 2030.2 This increase is driven by an ageing population, rising levels of obesity and the increasing use of tobacco and alcohol in both the developing and the developed world. The treatment of cancer is therefore a growing market. The market value was around US$50 billion in 2009, an increase of about 8 % on 2008, and about 40 % of this represented US sales.3
What are Cytotoxic Drugs?
Cytotoxic drugs were the first form of cancer chemotherapy to be established. They act by destroying rapidly dividing cells. The earliest use of cytotoxics can be traced back to nitrogen mustard, which was used to treat squamous cell carcinoma.1 Nitrogen mustard was derived from mustard gas and developed (but never used) as a poisonous gas in World War I. It is thought that it was first used to treat cancer as early as 1942. In results published in 1946, patients with haematopoietic disorders, including Hodgkin’s disease, lymphosarcoma and leukaemia, showed improvements after treatment with nitrogen mustard; some were even able to go back to work. Nitrogen mustard was most effective in treating Hodgkin’s disease, with one patient showing a good response for 33 months.4–6 Cytotoxic drugs have been used for many years and most physicians are used to handling them. There is a large amount of data on their safety and efficacy, and a wide range of combination regimens for many different types of cancers. These drugs also tend to be low-cost because many of them are available in generic forms.
The main groups of cytotoxic drugs are:
  • alkylating agents;
  • topoisomerase inhibitors;
  • anthracyclines and other cytotoxic antibiotics;
  • antimetabolites; and
  • antimicrotubule or antitubulin agents.

This first section of the article provides a brief introduction on the action of the different types of cytotoxic agents.
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Keywords: Antigens, cancer, cytotoxics, drug delivery, monoclonal antibodies, targeting