Signal Detection of Docetaxel in Canadian Spontaneous Adverse Event Reports (original) (raw)

Introduction: Cancer is one of the most widespread and feared diseases in the world today-feared largely because it is known to be difficult to cure. The main reason for this difficulty is that cancer results from the uncontrolled multiplication of subtly modified normal human cells. One of the main methods of modern cancer treatment is drug therapy (chemotherapy). Docetaxel is a clinically well established anti-mitotic chemotherapy medication (that is, it interferes with cell division). It is used mainly for the treatment of breast, ovarian and non-small cell lung cancer. Docetaxel has an FDA approved claim for treatment of patients who have locally advanced or metastatic breast or non small-cell lung cancer who have undergone anthracycline-based chemotherapy and failed to stop cancer progression or relapsed and a European approval for use in hormone-refractory prostate cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of 1 mole docetaxel per mole tubulin in microtubules. This binding stabilises microtubules and prevents depolymerisation from calcium ions, decreased temperature and dilution, preferentially at the plus end of the microtubule. Docetaxel has been found to accumulate to higher concentration in ovarian adenocarcinoma cells than kidney carcinoma cells, which may contribute to the more effective treatment of ovarian cancer by docetaxel. It has also been found to lead to the phosphorylation of oncoprotein bcl-2, which is apoptosis blocking in its oncoprotein form. Most common adverse reactions across doctaxel indications are infections,, myalgia but flushing is reported in very minor category of hypersentivity reaction. Objective: Major objective of this study was extract to Canadian Adverse Reaction Monitoring Program (CADRMP) database for possible toxic signal detection (SD) of docetaxel, evaluate the frequency of the flushing associated with it in different stratified groups for a putative signal, and generate awareness in healthcare professionals regarding usefulness of SD. Materials and Methods: Appropriate statistical methods were used for Adverse drug reaction (ADR) signal detection such as, proportional reporting ratio (PRR); reporting odds ratio (ROR); the Chi-square (X 2) statistic method; the 95% confidence interval (CI); the observed to expected ratio (O/E); and Du Mouchel method were used to calculate the possible signals. Significance of X 2 and other calculated statistics, e.g., PRR and ROR, was based on a composite criterion of regulatory guidelines and not on any particular statistical level of significance. Results: Calculated statistics by different methods were compared with regulatory criteria of a statistic value = 4.0 for X 2 , and =3.0 for the rest for SD to be declared significant. The PRR statistic was found to be 4.1330; by the ROR method it was 4.3866; the X 2 statistic was 205.0988, whereas the lower and upper limits of 95% CI of PRR were found to be 1.2133and 1.6247, respectively, by the O/E ratio was found to be 3.6780, and PRR with the help of Du Mouchel was found to be 3.6772. Thus, the flushing–docetaxel.Signals calculated in this study were significant. Conclusions: The therapeutic class specific signal of flushing associated with docetaxel was found potent enough to cause flushing.