More effective and less toxic treatment for breast cancer patients could be on its way, led by the work of Indonesian scientists presented at the World Congress of Pharmacy and Pharmaceutical Sciences today. Researchers from the Faculty of Pharmacy at the University of Indonesia have developed and validated a combined liquid chromatography-mass spectrometry (LC-MS/MS) method to analyse levels of metabolites of two cancer drugs tamoxifen and doxorubicin.
In the case of tamoxifen, reduction of cancer recurrence occurs via the presence of the metabolites endoxifen (END) and 4- hydroxytamoxifen, with the presence of END depending on a patient’s CYP2D6 genetic status. “Tamoxifen is effective if a threshold blood concentration of END of 3.3ng/ml is achieved. This study showed that we can use LCMS/MS to determine if therapy is effective and, therefore, we would know when adjustment of a dose is needed to make this treatment effective. This could be an improvement over current practice, which depends on checking oestrogen and progesterone receptor status and the stage of cancer, which is more diagnostic than therapeutic,” said lead researcher Professor Yahdiana Harahap. “In previous research the analysis used plasma. In this study, dried spot blood was used, which is more comfortable for patients,” she added.
In the case of doxorubicin, the accumulation of the main metabolite doxorubicinol is responsible for damaging the heart. The researchers performed fingerprick tests on 25 patients and were able to show that LC-MS/MS can rapidly and accurately determine levels of the metabolite 40 minutes after a dose of doxorubicin. “The doxorubicin metabolite is not currently used as a predictor of whether or not doxorubicin can be used daily by breast cancer patients, but there is potential in therapeutic drug monitoring. Prospective research could also be conducted to assess whether this doxorubicin metabolite affects the response rate of breast cancer chemotherapy,” said co-author Dr Ramadhan Ramadhan, of the functional medical staff of surgical oncology, Dharmais Cancer Hospital, Jakarta, Indonesia.
Professor Michael Ward, co-chair of the FIP Congress Programming Committee said: “This research shows how pharmaceutical science research could be applied in practice to individualise chemotherapy or for therapeutic drug monitoring that could increase the survival rate of breast cancer patients.”