Degradation and inactivation efficacy of ozone water for antineoplastic drugs in hospital settings

Purpose Occupational exposure to antineoplastic drugs in hospital settings is recognized to be hazardous, and as such environmental decontamination including degradation and inactivation of such drugs is recommended. To data, although various agents such as oxidants have been reported to be useful for decontamination, simpler, safer, and more convenient methods are required. In this study, the degradation and inactivation efficacy of ozone water, which has newly been introduced for decontamination of antineoplastic drugs in spills, was investigated for formulations of gemcitabine, irinotecan, and paclitaxel. Methods Antineoplastic formulations (medicinal ingredient: ∼1.5 μmol) were mixed with 50 mL of ozone water (>4 mg/L). The reactions were monitored by high-performance liquid chromatography, and the degradation mixtures were analyzed by 1H nuclear magnetic resonance spectroscopy in order to obtain the structural information of the degradation products. The formulations of gemcitabine and irinotecan and those degradation mixtures were evaluated for their mutagenicity using the Ames test and cytotoxicity against human cancer cells. Results gemcitabine and irinotecan were found to be readily degraded by the ozone treatment, and their active sites were suggested to be degraded. In contrast, paclitaxel was hard to be decomposed, possibly owing to the consumption of ozone by the polyoxyethylene castor oil added as a pharmaceutical additive of the formulation. No significant mutagenic changes of Salmonella typhimurium strains used for the Ames test were observed for the samples within the concentration ranges examined. The ozone treatment showed obvious increases in cell viability for gemcitabine formulation, and mild increases for irinotecan formulation. Conclusions Ozone water was shown to be effective as a decomposition agent for the antineoplastic drug formulations examined, although the efficacy depends on the chemical structures of the drugs and the pharmaceutical additives. It was also suggested that ozone treatment has a tendency to decrease the toxicity of the antineoplastic drug formulations. As such, further studies are required in order to clarify the effects and application limitations of ozone water.

Antineoplastic prescription among patients with colorectal cancer in eight major cities of China, 2015–2019: an observational retrospective database analysis

ObjectivesIt is unclear what is driving rising colorectal cancer (CRC) treatment costs in China, whether an adjustment in drug prices changes use and total cost. This study aims to estimate trends in drug use, prescribing patterns and spending for antineoplastic drug therapies for CRC in major cities of China.MethodsInformation from 128 811 antineoplastic drug prescriptions in CRC was retrospectively collected from the Hospital Prescription Analysis Cooperative Project. The prescriptions extracted included demographic information of patients, the generic name and the price of antineoplastic drugs. The Mann-Kendall and Cochran-Armitage trend test was used to estimate the trends of antineoplastic agent usage.ResultsThe number of antineoplastic prescriptions ranged from 18 966 in 2015 to 34 219 in 2019. Among the prescriptions collected in this study, the annual cost of antineoplastic drugs increased by 117.2%, and average prescription cost increased by 20%. Throughout the study period, the most prescribed antineoplastic drugs were capecitabine, oxaliplatin, fluorouracil and irinotecan, representing 49%, 27%, 21% and 9% of (per cent of visits (PV)). The PV of bevacizumab and cetuximab increased by 494% and 338% (from 1.8% and 1.3% in 2015 to 10.7% and 5.7% in 2019). In prescribing patterns of antineoplastic agents, monotherapy gradually decreased, while combination therapy, especially three-drug combination, increased significantly from 1.35% to 7.31%.ConclusionThis study estimated recent trends of antineoplastic drug use and expenditure for Chinese patients with CRC. These results would inform CRC treatment decisions, including health insurance negotiation, precision therapy access, allocation of research funding and evaluation of the financial burden of CRC drug treatment.

Blood contamination of the pharmaceutical staff by irinotecan and its two major metabolites inside and outside a compounding unit

Background Caregivers in healthcare settings are exposed to a risk of antineoplastic drug contamination which can lead to adverse health effects. Biological monitoring is necessary to estimate the actual level of exposure of these workers. This study was conducted with the aim of assessing blood contamination levels by irinotecan and its metabolites of pharmaceutical staff operating inside and outside a compounding unit. Methods The study took place within the pharmaceutical unit of a French comprehensive cancer centre. Blood samples were collected from the pharmacy workers operating inside and outside the compounding unit, and analysed by UHPLC-MS/MS. Plasma and red blood cell irinotecan and its metabolites (SN-38; APC) were determined with a validated analytical method detection test. Results A total of 17/78 (21.8%) plasma and red blood cell-based assays were found to be contaminated among staff. Overall, the total number of positive assays was significantly higher for staff members working outside the compounding unit than for workers working inside it ( P = 0.022), with respectively 5/42 (11.9%) and 12/36 (33.3%) positive assays. For plasma dosages, the “outside” group had a significantly higher number of positive assays ( P = 0.014). For red blood cell-based assays, no significant difference was found ( P = 0.309). Conclusions This study reveals that pharmaceutical staff serving in health care settings are exposed to a risk of antineoplastic drug contamination, not only inside the compounding room but also in adjacent rooms. The results would help to raise awareness and potentially establish protective measures for caregivers working in areas close to the compounding room as well.