Despite new and promising research about additional techniques in the battle against cancer, chemotherapy remains, together with radiotherapy and surgery, one of the most important therapies to help patients. Cytostatics offer the possibility to oppose to metastasis outside the surgical or radiotherapeutic region. Unfortunately, great toxicity is inherent to these substances.
Anthracyclines are among the most active antineoplastic agents. They are used –often in combination with other cytostatics- as standard treatment for haematological malignancies, such as acute leukemias, lymphomas and myeloma and solid tumors such as advanced and metastatic breast cancer, small cell long cancer, neuroblastoma and sarcoma. Haematological side effects are frequent but can often be resolved. Mucositis is unpleasant for patients but only seldom dose-limiting. The use of the anthracyclines is mainly limited by cardiotoxic side effects, of which the grade is often unpredictable and individual. Acute and reversible cardiac disorders are common. Chronic, potentially life-threatening congestive heart failure can develop several months after therapy.
Up to now, the body surface area is the only parameter used for calculating the dosage to be administered. To enhance efficacy of the treatment and limit the toxicity, there is a need for Therapeutic Drug Monitoring (TDM). My research is focused on the bioanalytical search for the predictive value of levels of anthracyclines and metabolites in blood and saliva, and of the unbound fraction in blood.
The samples, provided by the Ghent University Hospital, will be analysed by HPLC (High-Performance Liquid Chromatography), coupled to a fluorescence detector or mass spectrometer. The results of the blood sample analysis will allow the calculation of AUC, AUC for the free fraction, Css and Cmax values.
These data of the target compounds and of their relevant metabolites will then be evaluated in view of their predictive value for lowering the toxicity and enhancing the efficacy of a treatment. In addition, the eventual relationship between the free fraction in the blood and the level of that compound in saliva will be evaluated.Together with the analysis of the chemotherapeutic drug in biological matrices the status of the patients will also be recorded by the Department of Oncology of the Ghent University Hospital using the Common Toxicity Criteria (CTC). This will allow to find what parameter correlates best with the overall status of the patient. For different groups of patients treated with the same chemotherapeutic agent, limits will be established in view of reduction of the toxicity and of enhancing the therapeutic efficacy.
(By Kristof Maudens)
Taxanes are substances derived or originating from Taxus species. Two of the most important taxanes in the area of oncology are docetaxel (Taxotere®)and paclitaxel (Taxol®). Both are succesfully used to threat patients with cancer. As most chemotherapeutic agents these substances bear toxic properties, which cause serious side effects. Clinically, myelosuppression seems to be the most harmfull effect, as this can even be dose limiting.
As an analytical research laboratory, we are developping a HPLC-MS method for the quantification of both taxanes in blood. Using this method, our goal is to develop a Therapeutic Drug Monitoring scheme to improve the therapy. Side effects, sometimes livethreatening, are hoped to be avoided in this way. In addition, underdosing of the patient, e.g. by a higher metabolism, can be anticipated, resulting in a more effective therapy.
Useful internet links about taxanes:
(By Kjell Mortier)