Adverse reactions to docetaxel: an active survey (original) (raw)
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Cancer Chemotherapy and Pharmacology, 2017
, from Jan 2013 to Mar 2016. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Results Significant product-related differences were observed in the following non-hematological adverse events: injection site reaction (P = 0.0012), hand-foot syndrome (≥grade 3) (P = 0.0003), and oral mucositis (≥grade 3) (P = 0.0080). Multivariate logistic regression analyses of the associations between these adverse events and the total additive administered (g/m 2) identified significant negative effects of PS80 and ethyl alcohol. Conclusions Injectable docetaxel products had different adverse event profiles, which showed negative associations with the amounts of PS80 and ethyl alcohol present. This finding indicated that there might be additive-related pharmacokinetic and physiochemical differences among these products, suggesting a need for further pre-or post-approval testing of injectable generic products containing noticeable different levels of additives.
Breast care (Basel, Switzerland), 2018
The present study reports on the efficacy and safety of adjuvant docetaxel in real-life patients with early-stage breast cancer. This is a prospective, multicenter, post-marketing study that evaluates the efficacy and safety of docetaxel-based regimens in patients with early breast cancer treated between 2007 and 2012. A total of 698 female breast cancer patients receiving adjuvant docetaxel-based regimens were included in this study. Docetaxel monotherapy was administered in 4.2%, whilst most patients received polychemotherapy. Non-hematological adverse events included skin reactions in 32.7% of the subjects. Multiple adverse events were reported and most commonly included asthenia (66.5%), alopecia (43.4%), and diarrhea (24.2%). It is noteworthy that no fatal toxicities occurred. Several hematological adverse events were reported during treatment, with anemia being the most common. The results of this real-life experience, characterized by a relatively large sample size and long f...
Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 2020
Docetaxel is an effective treatment approved for many types of cancers, but its effectiveness in clinical practice can be compromised by significant occurrence of adverse drug reactions. The aim of the current study was to measure the distribution of adverse drug reactions of docetaxel reported in Iraq and to assess the causality, severity, seriousness, preventability, expectedness and outcome of these adverse reactions. A retrospective study conducted on individual case safety reports from the Iraqi Pharmacovigilance Center / Ministry of Health. The study included 118 individual case safety report containing 236 adverse drug reactions.Most of the adverse drug reactions were related to skin and subcutaneous tissue disorders(26.7%), followed by respiratory, thoracic and mediastinal disorders (20.8%), gastrointestinal disorders (17.4%) and general disorders and administration site conditions (10.6%). The majority of these reactions with possible causality (68.6%), moderate severity (7...
Signal Detection of Docetaxel in Canadian Spontaneous Adverse Event Reports
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.
Toxicities of docetaxel: original drug versus generics—a comparative study about 81 cases
SpringerPlus, 2016
Introduction: Docetaxel is a chemotherapy drug widely prescribed in oncology that recognizes a variety of manufactured generics whose toxicity is increasingly reported. The aim of this study was to compare the toxicities between the original and a generics docetaxel in a Moroccan center. Methods: In a cross sectional study, we enrolled patients treated with docetaxel from the oncology department of the military hospital of Rabat over a period of 2 years (2013-2014). We compared the prevalence of hypersensitivity reactions, febrile neutropenia, peripheral neuropathy, gastrointestinal, cutaneous, and hematologic toxicities, between four different presentations of docetaxel including the original drug. Only grade II or worse adverse events related to chemotherapy were considered. Treatments discontinuations due to toxicity were also compared. Unusual skin toxicities were included. Results: 81 patients were eligible for analysis [43/generics arm vs. 38/original drug arm. Hematological toxicity was significantly more frequent in the generic arm than in the original drug (32.6 vs. 13.2 %; p = 0.04)]. Also, a signifying higher rate of treatment discontinuation was observed in the generic arm (39.5 vs. 7.9 %, p = 0.001). The use of specific generic increase numerically the skin toxicities (17.6 vs. 0 %, p = 0.026). Conclusion: Our data suggest that generics of docetaxel are associated with an increase of hematological and cutaneous toxicities, an increase of treatment discontinuation rate and emphasize the need of a regulation of generics' manufacture.
Supportive Care in Cancer, 2013
Purpose-As the result of a recent national shortage in paclitaxel, some patients who were receiving or scheduled to receive weekly paclitaxel were converted to every 3-week (q3w) docetaxel with granulocyte colony-stimulating factor support. Our institution noted higher than expected incidence of severe skin toxicity events attributable to docetaxel during the shortage period among our breast cancer patients. In this report, we summarize the clinical course of the first five cases, review the literature surrounding docetaxel-induced skin toxicity, and offer possible prevention and treatment strategies to improve docetaxel tolerability. Methods-The observation period for this case series was August 1 through October 21, 2011. All patients treated with docetaxel were identified from our electronic medical record. Operable stage I-III breast cancer patients who received ≥1 dose of docetaxel monotherapy at 75-100 mg/ m 2 q3w were included in this study. The cases of grade 3-4 docetaxel-induced skin toxicities identified by the treating oncologists were then contacted and signed an informed consent through an Institutional Review Board-approved protocol. Results-Thirty-four patients met the inclusion criteria. Five patients (14.7 %) experienced grade 3 skin toxicity events attributable to docetaxel, a significantly higher rate than previously reported for docetaxel dosed at 75-100 mg/m 2. Conclusions-Docetaxel-induced dermatologic toxicity is well characterized; nonetheless, its etiology is largely unknown and evidence-based prevention and management strategies are lacking. This report shows that the use of docetaxel 75-100 mg/m 2 q3w subsequent to dose-dense doxorubicin and cyclophosphamide regimen can lead to unacceptable rate of severe skin toxicity.
Hypersensitivity Reactions to the Taxanes Paclitaxel and Docetaxel
Clinical Drug Investigation, 1997
Paclitaxel and docetaxel are taxane derivatives with a significant antitumour activity. For both drugs, a high incidence of hypersensitivity reactions (HSRs) has been observed during the initial clinical development. However, current pretreatment regimens, consisting of corticosteroids and antihistamines, have led to a substantial decrease in major HSRs. In this study, we describe a case series of 9 out of a total of 415 patients from eight different taxane studies who received either paclitaxel or docetaxel and experienced severe HSRs, despite the use of premedication. Five of these 9 patients had allergies or atopy. We observed an increase in blood pressure during the HSR in 5 patients, whereas a decrease was anticipated. Retreatments, with additional corticosteroids, antihistamines and in some cases a lower infusion rate, were performed successfully in 7 patients. One of these patients was given, after two courses with HSR symptoms, sodium cromoglycate as prophylaxis, after which she received four successive courses without symptoms of HSR.
A dose escalation study of weekly docetaxel in patients with advanced solid tumors
Cancer Chemotherapy and Pharmacology, 2000
Purpose: To determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of weekly administration of docetaxel for three consecutive weeks every 4 weeks in patients with advanced solid tumors. Patients and methods: A total of 26 patients with malignant tumors refractory to conventional treatment were enrolled in this phase I study; their median age was 62 years. Of the 26 patients, 16 (62%) had previously received more than one chemotherapy regimen and 17 (65%) had previously received taxanes in a 3-week schedule. Docetaxel was administered after appropriate premedication at escalating doses (starting dose 30 mg/ m 2 ) as a 1-h i.v. infusion for three consecutive weeks in cycles of 4 weeks. Results: A total of 68 chemotherapy cycles were administered with a median of three cycles per patient (range one to six). The DLT was reached at 45 mg/m 2 per week and the dose-limiting events were grade 4 neutropenia, febrile neutropenia, and treatment delay due to incomplete hematologic recovery. The MTD was de®ned at a dose of 42 mg/m 2 /week. Grade 3/4 neutropenia occurred in seven patients (27%) (10% of cycles), and four patients (15%) developed febrile neutropenia. There were no deaths due to sepsis. Grade 2 peripheral neurotoxicity was observed in two patients (8%), grade 2 and 3 fatigue in 14 (54%), grade 2 edema in seven (27%), mild allergic reactions in two (8%) and lacrimation in three (12%). One (4%) complete response and eight (35%) partial responses (overall response rate 39%) were observed in 23 evaluable patients. Stable disease and progressive disease were observed in six patients (26%) and eight patients (35%), respectively. All responses were observed in patients with metastatic breast cancer, one of whom had progressed on paclitaxel-based and two of whom had progressed on docetaxel-based chemotherapy. Conclusions: The weekly administration of docetaxel for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity pro®le, and can be given on an outpatient basis. Moreover, this schedule of docetaxel administration seems to have an enhanced ecacy, especially in patients with advanced breast cancer who have failed front-line taxane-based chemotherapy.
The study is the assessment of Adverse drug reaction in a Cancer Care Center. We have conducted the prospective study to analyse the ADR The study population consisted of 178 patients in total. Among them 59% (n=105) of the patients were females. On classifying the patients based on age 33.15% (n=59) of the patients were of age group 60-69. From the total prescription 37.64% (n=67) of the diagnosis was concerned with the reproductive system and in 28.65% (n=51) of the cases the site of tumor was the cervix. As a part of the chemotherapy the patients were prescribed with various classes of anti-cancerous agents. About 67.97% (n=121) alkylating agents were preferred. And most frequently used anti-cancer drug was 5-FU. In 23.59% (n=42) of patients with a combination cisplatin + 5-FU was prescribed. 34.83% (n= 62) of patients had been prescribed with quinolones and 19.66% (n=35) of cases were given with ofloxacin. The prescriptions contained drugs other than anti-cancer agents like nutritional supplements. 35.39% (n=63) of the prescriptions were prescribed with Iron supplements. On classifying the ADRs found according to Wills & Brown classification of ADR assessment, 45.89% of the ADRs were of Type A(Augmented reaction) the chemotherapeutic drugs have a narrow therapeutic index and the dosage needed to achieve a therapeutic response usually proves toxic to the body’s rapidly proliferating cells. Early modifications in dosage regimen of chemotherapeutic agents may minimize the hazardous ADRs. Through pharmacist intervention in the adjustment of dosage regimen and supportive care maximum benefits can be gained by the patients because supportive care improves patient comfort and improves quality of life. Keywords: ADR, Pharmacist Intervention, Supportive care.
International Journal of Basic and Clinical Pharmacology, 2016
Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed (second most common cancer overall). 1 With rising incidence and awareness, breast cancer is the commonest cancer in urban Indian females, and the second commonest in the rural Indian women. 2 Both the morbidity and mortality are high in India with an estimated 70, 218 deaths. 1 Such high mortality rate can be attributed to the lack of adequate knowledge about breast cancer at the root level leading to delay in approaching the medical services and lack of sufficient medical facilities at all levels. This study was concerned about the adverse reactions associated with neo-adjuvant and adjuvant chemotherapy given to breast cancer patients. The various drugs available include paclitaxel, docetaxel, adriamycin, cyclophosphamide, 5-flurouracil, each having its own profile of adverse reactions. The use of combination chemotherapy has been associated with increased response rates as compared with a single agent. 3 The common drug combinations adopted in our government setup was paclitaxel, adriamycin, cyclophosphamide (PAC) and 5-flurouracil, adriamycin, cyclophosphamide (FAC). Paucity of data exists regarding the adverse reactions of these drug regimens adopted in TVMCH. This study was therefore undertaken to compare and ABSTRACT Background: The incidence of breast cancer is increasing in India. A combination of medicines is typically used to treat breast cancer. All the medications used in treatment are associated with various side effects. So this study is done to estimate and compare the adverse reactions of taxol and nontaxol based chemotherapy regimens in breast cancer patients attending Tirunelveli Medical College Hospital. Methods: The study was conducted in the oncology ward at TVMCH for a period of 60 days from August 2 nd October 2 nd 2014. Patients with unilateral or bilateral carcinoma breast with or without metastasis, receiving chemotherapy were included. Medication details such as the type of regimen, dose, and duration of regimen and relevant data of lab investigations were collected. 30 patients who fulfilled study criteria were included, out of which 16 were assigned FAC (5flurouracil, adriamycin, cyclophosphamide) regimen and 14 were assigned PAC (paclitaxel, adriamycin, cyclophosphamide) regimen. Results: The incidence of adverse reactions like myelodepression resulting in Neutropenia (64.28%), Anaemia (57%) and Thrombocytopaenia (21%) was comparatively higher with PAC regimens than FAC regimen. Nausea (75%) and vomiting (43%) was found to be higher with FAC regimen despite antiemetic use. No serious adverse reactions occurred in either regimens. Conclusions: The adverse reaction profile of FAC regimen was found to be favourable than PAC therapy though not statistically significant, with no references to efficacy and potency of these regimens in the treatment of breast cancer patients with or without metastasis.