Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Erbitux (Alphapharm)
2 mg/mL in 50 mL vials
Approved indication: metastatic colorectal cancer
Australian Medicines Handbook section 14.3.4

Antineoplastic antibodies such as rituximab and trastuzumab act on cancer cells by binding to target antigens.1 Cetuximab is a genetically engineered chimeric monoclonal antibody which binds the epidermal growth factor receptor. The gene for this receptor is over expressed in many patients with colorectal cancer and is associated with a poor prognosis. By binding to the receptor, cetuximab blocks the action of epidermal growth factor with the aim of reducing the growth and viability of tumour cells.

Cetuximab is given by a slow intravenous infusion once a week. The pharmacokinetics of cetuximab vary with the dose. At higher doses there is a decreased clearance and increased half-life. At the recommended doses cetuximab has a half-life of 80-120 hours.

A randomised, open-label trial compared cetuximab alone or in combination with irinotecan in 329 patients with metastatic colorectal cancer. All the patients had tumours with epidermal growth factor receptors and their tumours had progressed despite previous treatment with irinotecan. Approximately 11% of the patients given cetuximab and 23% of the patients given the combination had some response to treatment, as judged by imaging studies. Although the median time for the disease to progress was longer with the combination (4.1 months versus 1.5 months), this therapy had no significant survival advantage over cetuximab alone. The median survival was 8.6 months with combination therapy and 6.9 months with monotherapy.2

During the study 80% of the patients developed an acne-like skin reaction. This was severe in 5.2% of the patients taking cetuximab and in 9.4% of those taking cetuximab with irinotecan.2 Premedication with an antihistamine is recommended because of the risk of a hypersensitivity reaction to an infusion of cetuximab. Dyspnoea has developed in 25% of patients given cetuximab. This has been severe in approximately 10% of patients. Those given cetuximab in combination with irinotecan are prone to diarrhoea and neutropenia. Blocking the epidermal growth factor receptor may delay wound healing.

After irinotecan has failed adding cetuximab induces a greater response than giving cetuximab alone. This suggests that cetuximab somehow enhances the effect of irinotecan. There is therefore a need to compare cetuximab with other drugs, such as oxaliplatin, which can be given to patients with irinotecan-refractory disease.

Although cetuximab has been approved for monotherapy and for use in combination with irinotecan, combined therapy is more likely to be useful for metastatic disease that has progressed. Cetuximab should not be prescribed for patients whose colorectal tumours do not have over expression of the epidermal growth factor receptor.

manufacturer did not respond to request for data

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.