| Ch 11 | Page 8 / 16 | |
| Cancer other treatments |
Trastuzumab | |
Trastuzumab (Herceptin™) is one of the major developments in the treatment of breast cancer over recent years, but unfortunately only less than a quarter of patients can benefit from it.
There is an entire family of HER receptors.
Trastuzumab is a mouse recombinant humanised monoclonal antibody IgG1. It reacts with HER2-Neu human growth factor receptors (ErbB2) which are overexpressed in breast cancer cells in approximately 20% of patients.
Overexpression of HER-2 is observed in 20 to 30% of primary breast tumours. Studies have shown that women with tumours overexpressing this receptor have a shorter survival than those with tumours which do not overexpress it.
Trastuzumab inhibits the proliferation of tumour cells overexpressing HER-2. Another mechanism of action is its major stimulation of antibody dependent cell cytotoxicity (ADCC).
Trastuzumab should only be used among patients whose tumours overexpress HER-2. For other patients, the antibody is totally inefficient and can even be toxic for normal tissues.
The overexpression of HER-2 is detected by immunohistochemistry (IHC) on sections of fixed tumours. Patients who may benefit from Trastuzumab have an immunohistochemistry score of 3+ or a strong amplification as demonstrated by the FISH technique (Fluorescence In situ Hybridisation).
An increasing number of pathology laboratories are now producing reproducible and reliable immunohistochemistry results. Experts recommend an interpretation diagram in order to evaluate the intensity of the coloration of the membrane in relation to the increased number of receptors. If more than 10% of the cells are concerned, the slide should be classified as 3+.
The plasma half-life of trastuzumab is around 28 days. This relatively long duration is explained by the ‘humanised’ nature of this antibody without immunogenic reaction. Thus, the recommended rhythm of injections is once every 3 weeks. The starting dose is 4 mg/kg, followed by a maintenance dose of around 2 mg/kg per week.
The response rate of patients overexpressing HER-2 is over 50%. The responses are long-lasting (several months to two to three years) in patients with cancers which are resistant to usual chemotherapy.
This product is only used among patients overexpressing HER2. Up to very recently, it was also only used in metastatic cancer.
As a single therapy, it is used for patients failing to respond to two different chemotherapy protocols, with at least one protocol containing anthracyclins and taxane.
Patients having received hormonal therapy, should be relapsing after this treatment modality.
In association with paclitaxel, in patients previously untreated by chemotherapy for their metastatic disease and for whom anthracyclin treatment cannot be instituted.
Numerous studies are currently in progress and will modify these indications in the following months or years.
In most patients, trastuzumab is remarkably well tolerated.
Some immediate hypersensitivity reactions may be observed: fever, dyspnoea, hypotension, rashes. Generally these reactions occur during the first infusion and do not recur afterwards, following simple antipyretic treatment.
More rarely, severe hypersensitivity reactions with shock, pulmonary oedema and severe cardiopulmonary insufficiency may be observed (among which, a few observations involving toxic death).
Cardiac toxicity has been observed in patients previously treated with anthracyclins. Cardiac function should therefore be evaluated before any treatment, and then regularly every 8 to 10 weeks. Cardiotonic treatment may be prescribed to correct this insufficiency if the therapeutic benefit of trastuzumab is impressive. Otherwise, trastuzumab should be stopped.
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