November 24, 2010
Cough Medicine’s Key Lesson For Breast Cancer Patients
(Ivanhoe Newswire) -- Cough medicine could be used as way of predicting how well individual patients metabolize tamoxifen used in the treatment of their breast cancer, according to a new study.
The findings suggest that it could be possible to use cough syrup as a probe, which would enable doctors to identify patients with altered metabolism and use this information to improve individual treatment, making it more effective and reducing the chances of side-effects.
Tamoxifen, which is widely used both to treat and prevent breast cancer, is metabolised by the body into endoxifen, which is responsible for the drug's anti-cancer activity and which can cause tamoxifen-related side-effects. Two enzymes, CYP2D6 and CYP3A, are responsible for metabolising tamoxifen into endoxifen, and the metabolite forms only if there are sufficient quantities of these enzymes.
Mrs Anne-Joy de Graan, a PhD student in the medical oncology department at the Erasmus Medical Centre in Rotterdam (The Netherlands), who presented the study, explained: "At present, all patients treated with tamoxifen in The Netherlands are prescribed a fixed dose of 20 mg or 40 mg. But there is a large difference in the toxicity (for example, hot flushes, endometrial cancer and thrombosis) and efficacy of this agent. This is thought to be the result of variance in endoxifen concentrations between patients. Recently, research has focused on whether this variation in endoxifen levels is caused by patients' individual genetic make-up. We know that there are genetic variations that cause women to be 'poor metabolisers'. This means that these women cannot form enough endoxifen due to absence of CYP2D6 enzymatic activity." In addition, other factors can influence a way a woman metabolises tamoxifen, such as CYP3A enzymatic activity, the use of other medicines, alcohol consumption and smoking.
Mrs de Graan and her colleagues at Erasmus studied the use of dextromethorphan, the active ingredient in cough suppressant medicine, in 40 breast cancer patients who had been taking tamoxifen for more than three weeks. Dextromethorphan is metabolized in the same way as tamoxifen and is harmless to the patient. "It is a so-called "Ëprobe' drug, a harmless substance that can be used to predict the metabolism of another drug. We used dextromethorphan to evaluate its use as a probe drug for tamoxifen metabolism," Mrs. De Graan was quoted as saying.
"We believe that tailored therapy will optimise treatment with systemic therapy. The current dosing strategy does not take individual differences into account like co-medication, DNA difference, life-style factors like smoking behaviour, and alcohol consumption. Genotyping tamoxifen-treated patients is just one step towards individual treatment, but different results are reported in the literature. We investigated another way of predicting tamoxifen metabolism by phenotyping, which takes various individual differences into account. Future research will tell which strategy for individualising treatment will be the best to implement in daily practice. Our dextromethorphan test could aid in future studies on the association of tamoxifen and CYP2D6 genotype and phenotype, and ultimately in the personalisation of tamoxifen treatment," concluded Mrs de Graan.
SOURCE: 22nd EORTC-NCI-AACR held in Berlin, Germany from November 16-19, 2010