Toxicities of docetaxel: original drug versus generics—a comparative study about 81 cases

Abstract

IntroductionDocetaxel 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.MethodsIn 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.Results81 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).ConclusionOur 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.

Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells

“…The synergy of the PAD2 inhibitor and docetaxel was also confirmed in tumor growth in vivo. High-dose docetaxel therapy was found to be associated with safety issues among clinical trial patients and effective strategies to decrease the dosage are urgently needed [5, 10]. Therefore, our drug regimen may provide a better therapeutic strategy to reduce the dose of docetaxel used for those patients with tamoxifen-resistant breast cancer in the future.…”

“…Clinical studies also showed that combination of docetaxel with other cancer drugs yields good results [5]. However, cumulative systemic toxicity after prolonged and high-dose therapy was found to be associated with safety issues among clinical trial patients including hematological issues, asthenia, cutaneous reactions, and neurosensory reactions [5, 10]. Clearly, it is of high clinical significance to enhance the efficacy of docetaxel using lower doses in a less toxic manner and to reduce its side effects.…”

Comparative In Vitro Toxicity Study of Docetaxel and Nanoxel, a Docetaxel-Loaded Micellar Formulation Using Cultured and Blood Cells

“…For instance, previous studies used Tween 80 and ethanol as vehicles for docetaxel, which are from marketed docetaxel (18,19), while 0.1% dimethyl sulfoxide was used as a vehicle in this study. Although Tween 80 and ethanol are generally regarded to be biocompatible, the combination of Tween 80 and ethanol is well known for its nonspecific toxicity and may enhance the toxicity of docetaxel (20,21). Further study is needed regarding the hemolytic properties of docetaxel and Nanoxel.…”

Docetaxel-Induced Stevens-Johnson Syndrome in a Patient with Metastatic Prostate Adenocarcinoma

“…There have been an increasing number of generic docetaxel toxicities in comparison to the original drug formulation. Impurities, excipients, and the amount of active agent itself can all have an impact on the efficacy of the drug and impact its narrow therapeutic index resulting in increased side effects [2].…”