Clinical Research Of The Feasibility To Reduce Adverse Reactions Of Docetaxel

Background The effective mechanisms of docetaxel are unique, which has been widely used as antitumor drugs in clinical by far. Its major adverse reactions are hypersensitivity reactions (HSRs), marrow inhibition, fluid retention, angioedema, neural toxic reaction and gastrointestinal reaction and etc. Among them, HSRs are the most serious problem in the clinical application. These reactions range in severity from mild flushing and itching to bronchospasm, dyspnea and significant alterations in blood pressure with loss of consciousness or not, and even to death. Nevertheless, HSRs are often reported sporadically only in clinical trials or as case reports. Meanwhile, the vague or inconsistent terminology used to describe these reactions may reflect our poor understanding about them. Although using dexamethasone pretreatment can reduce the adverse reactions, this treatment plan still has been controversial both at home and abroad. Additionally, the usage and dosage of dexamethasone haven't yet reached a consensus. At present, no studies were reported on the systemic pretreatment plan of docetaxel, especially in elderly people that the effectiveness and safety of the plan wasn't studied either.Objective First, to explore the efficacy of different dosages of dexamethasone in prevention and treatment of docetaxel HSRs. Second, to further investigate the effectiveness and safety of low-dose dexamethasone in prevention and treatment of docetaxel HSRs in elderly patients by modifyingModified Cumulative Illness Rating Scal.Methods 1.Clinical research on different doses of dexamethasone to prevent and cure HSRs of docetaxelA survey was undertaken on cancer patients who were administered with docetaxel in the department of oncology, the first affiliated hospital of Anhui Medical University from the October 2006 to September 2007. According to the order of admission, patients were quasi-randomized into two groups. The patients in the study group were received oral dexamethasone 4.5 mg twice a day continuing 3 days, while patients in the control group were received 8 mg.2.Clinical research on pretreatment regimen of low-dose dexamethasone to prevent and cure HSRs related to docetaxel in elderly cancer patients A survey was undertaken on cancer patients with weekly docetaxel and older than 65 years in the department of oncology, the first affiliated hospital of Anhui Medical University from the October 2007 to September 2008. According to the order of admission and the ratio of 3:2, older patients with weekly docetaxel were unequally randomized into two groups. Before treated, all of patients were scored by physicians referenced to the MCIRS. The patients in the study group received oral dexamethasone 4.5 mg once per day continuing 3 days, while patients received 8 mg in the control group.Dexamethasone was taken by patients for 3 consecutive days before docetaxel treatment. Each patient was given docetaxel chemotherapy no less than 2 cycles. HSRs and adverse reaction were judged according to the toxic criteria of CTCAE 3.0. All statistical analyses were done by the computer program SPSS 11.5. The difference of between two groups was compared by Chi-Square test or Fisher's exact test. P-values less than 0.05 were considered to be of statistical significance.Results 1.In the study on different doses of dexamethasone to prevent and cure HSRs related to docetaxel, there were 162 patients matching the condition, of which 17 cases had HSRs (the incidence rate was 10.5%). There were 90 patients in the study group and 72 patients in the control group, with a hypersensitivity reaction rate of 11.1% and 9.7%, respectively. There was no significantly statistical difference between them (P =0.774). The main symptoms were rash, fever/chills, angioedema, chest discomfort and blood pressure. And the major adverse reactions are neutropenia, hemoglobin, nausea and vomiting, reduce fatigue, humoral retention. There were no obvious differences about the incidence rate of these adverse reactions between two groups.2. In the study on pretreatment regimen of low-dose dexamethasone to prevent and cure HSRs related to docetaxel in elderly cancer patients, there were 91 patients matching the condition. Among them, there were 54 patients in the study group and 37 patients in the control group, with a hypersensitivity reaction rate of 7.4% and 8.1%, respectively. There was no significantly statistical difference between them (P =1.000). The main symptoms were rash/itchy 3.3%, angioedema 2.2%, fever/shivers 1.1% and chest discomfort 1.1%. According to the MCIRS grade: Between 14-point and 19-point groups, there were statistically significant differences on the symptoms both neutropenia and fatigue (P =0.027 and 0.048, respectively). This finding suggested that the incidence rate of neutropenia and fatigue might increase with the MCIRS score going up.Conclusion1.The pretreatment regimen of low-dose dexamethasone can reduce both the side effects and the hypersensitive reaction and adverse reaction. In the prevention and treatment of docetaxel HSRs, there was no predominance between the pretreatment regimen of regular-dose dexamethasone and that of the low-dose.2.In elderly patients, adverse reactions are positively correlated with MCIRS scores. With the scores increasing, the pretreatment regimen of low-dose dexamethasone has the similar safety and efficacy compared with that of the regular-dose.