Reducing renal function assessment prior to platinum-based chemotherapy: a real-world evaluation.

BACKGROUND: Platinum-based chemotherapy, a widely used backbone of systemic cytotoxic anticancer treatment, is associated with nephrotoxicity. Currently, renal function is generally assessed prior to each administration of cisplatin or carboplatin, but there is no guideline regarding the frequency of renal function determination. OBJECTIVE: The primary objective was to determine the median time to a clinically relevant dosage adjustment (>10%) due to change in renal function in patients treated with cisplatin and carboplatin. Secondly, variables influencing changes in renal function were assessed. METHODS: We conducted a retrospective analysis of serial renal function assessments in platinum-treated patients with cancer in two academic medical centers, using a query to extract data from the electronic health records between 2017 and 2019. RESULTS: In total, 512 patients receiving cisplatin and 628 patients receiving carboplatin were included. In total, 15% of all cisplatin-treated patients were found to have a renal function less than 60 mL/min at least once during treatment, with a median time to renal function decline of 67 days (range 5-96 days), which did not differ between treatment regimens. For carboplatin 21% of patients were found to have had a dosage variation of more than 10% at least once during treatment, with a median time-to-event period of 64 days (range 5-100 days). INTERPRETATION: Dose adjustments during platinum-based chemotherapy resulting from renal function decline occur after a median time of ≥64 days. Our data provide substantiated guidance to recommend renal function assessment during platinum-based chemotherapy in clinically stable patients to once every 3 weeks.

Exclusion of Ranitidine From Premedication Regimens During Paclitaxel Treatment.

This cohort study conducted in the Netherlands uses electronic medical records to assess incidence of hypersensitivity reactions with and without H2-receptor antagonist premedication before paclitaxel administration.

Aggregate Formation and Antibody Stability in Infusion Bags: The Impact of Manual and Robotic Compounding of Monoclonal Antibodies.

Monoclonal antibodies (mAbs) can be damaged during the aseptic compounding process, with aggregation being the most prevalent form of degradation. Protein aggregates represent one of several risk factors for undesired immunogenicity of mAbs, which can potentially lead to severe adverse drug reactions and less effective treatments. Since data on aggregate and particle formation by robotic compounding is missing, we aimed to compare the antibody stability between robotic- and manual compounding of mAbs with regard to formation of (sub)visible aggregates. Infliximab and trastuzumab were compounded into infusion bags with the APOTECAchemo robot or manually by nurses or pharmacy technicians. The products were analyzed by quantifying (sub)visible particles with nanoparticle tracking analysis, dynamic light scattering (DLS), light obscuration, micro-flow imaging, high pressure size exclusion chromatography (HP-SEC), and visual inspection. HP-SEC showed high percentages monomers in trastuzumab (99.4 % and 99.4 %) and infliximab (99.5 % and 99.6 %) infusion bags for both manual and robotic compounding, respectively. DLS indicated more consistent and reproducible results with robotic compounding, and confirmed monodisperse samples with a higher polydispersity index for manual compounding (0.16, interquartile range; IQR 0.14-0.18) compared to robotic compounding (0.12, IQR 0.11-0.15). This study shows that the studied compounding methods had a minor impact on the number of aggregates and particles, and that robotic compounding of mAbs provided at least similar quality as manual compounding.

A Tool for Deprescribing Antithrombotic Medication in Palliative Cancer Patients: A Retrospective Evaluation.

Treating palliative cancer patients with antithrombotics is challenging because of the higher risk for both venous thromboembolism and major bleeding. There is a lack of available guidelines on deprescribing potentially inappropriate antithrombotics. We have therefore created an antithrombotics scheme to aid in (de)prescribing antithrombotics. A retrospective single-center clinical cohort observational study was performed to evaluate it. Patients with solid tumors with a life expectancy of less than 3 months seen by the palliative team were included. Comparisons were made between patients who were treated according to the antithrombotics scheme and those who were not. 47.6% of patients used antithrombotics. One hundred and eleven patients were included for analysis. Most patients used antithrombotics according to the scheme (n = 80, 72.1%). Eleven patients experienced a clinical event, seven patients in the scheme adherence group (9.9%) and four in the no scheme adherence group (13.8%), which was not statistically significant (p = 0.726). The higher frequency of clinical events in the group without scheme adherence suggests that (de)prescribing antithrombotics according to the antithrombotics scheme is safe. The results of this study suggest that the antithrombotics scheme could aid healthcare professionals identifying possible inappropriate antithrombotics in palliative cancer patients. Further prospective research is needed to investigate this tool.

Extending Practical (In Use) Shelf Life of Oncology Drug Vials Using Spikes.

The global increase of use of oncology drugs combined with the higher costs of these drugs raise the question of how to reduce these costs. One way to reduce the costs is to reduce spillage by extending the beyond-use date by preserving remainders in the vial of (expensive) oncology drugs instead of wasting them. Therefore, we investigated if spikes, instead of the expensive closed-system transfer devices, can be used to extend the beyond-use date of drugs both at room temperature and in the refrigerator during seven days after reconstitution and partial fluid withdrawal of a vial. Six hundred vials containing concentrated tryptic soy broth were reconstituted with 10-mL of sodium chloride 0.9%, after which approximately 3 mL were removed from the vial and discarded using a regular spike for 300 vials and a MicroSpike for the other 300 vials. Subsequently, the vials were stored either at refrigerator temperature or at room temperature for seven days. After seven days, all six hundred vials were transported and incubated at a temperature of 30°C to 35°C for fourteen days. None of the six hundred vials used showed contamination, either punctured with a MicroSpike or with a regular spike, after storage of seven days at room temperature or in the refrigerator and two weeks of incubation. Conclusively, it can be stated that hospital pharmacies play an important role in keeping the high costs of oncology drugs as low as possible. This study shows that using a spike instead of a more expensive closed-system transfer device for preservation of the remainder of oncology drugs will further reduce spillage of expensive drugs resulting in lower healthcare costs.

Analysis of production time and capacity for manual and robotic compounding scenarios for parenteral hazardous drugs.

BACKGROUND: The increasing amount of hazardous preparations in combination with shortages leads to a call for more efficient compounding methods. This research aims to evaluate the required amount of time, production capacity and direct labour costs of the manual, manual software-supported and robotic compounding of parenteral hazardous drugs. METHODS: This multicentre study was conducted at the clinical pharmacy departments of three Dutch hospitals with different compounding methods: St Antonius hospital (manual software-supported compounding), Amsterdam University Medical Centre (Amsterdam UMC) (both robotic compounding and manual compounding without software support) and OLVG (robotic compounding). Time measurements of individual hazardous drugs were performed in all three hospitals. At Amsterdam UMC and St Antonius hospital, the times per compounding phase, the production capacity and the direct labour costs per preparation were also determined. To reflect real-world situations, the combination of robotic and manual compounding was also studied. RESULTS: The total compounding process, including the actions before compounding and the release-time and cleaning time, lasted 6:44 min with robotic compounding and was faster than manual compounding with and without software support (6:48 and 9:48 min, respectively). The production capacity of one full-time equivalent (FTE) on 1 day (P1FTE1day) was 15 preparations per FTE per day with manual compounding with and without software support, and 57 preparations per FTE per day with only robotic compounding. If manual and robotic compounding were combined, the production capacity was 30 preparations per FTE per day. In this setting, the direct labour costs per preparation were €5.21, while these costs were €13.18 with only manual compounding. CONCLUSION: Compared with manual compounding, robotic compounding was faster over the total compounding process. A combination of manual compounding and robotic compounding could lead to 100% more preparations per FTE and 2.5 times lower direct labour costs compared with manual compounding.

The handling of biopharmaceuticals used in home-based therapy for cancer patients.

BACKGROUND: Due to their low bioavailability, biopharmaceuticals are typically administered via injection or infusion in a hospital setting. Home-based therapy could be a valuable alternative for cancer patients. However, when exposed to stressors, such as high or low temperatures, particles can form in the biopharmaceutical solution, compromising the safety and efficacy of the biopharmaceutical. AIM: This research investigated current practises with ready-to-administer biopharmaceuticals to determine if it is possible to offer cancer patients home-based therapy with monoclonal antibodies. METHODS: First, a questionnaire was conducted with the survey tool Survalyzer among Amsterdam UMC patients receiving immunoglobulins at home. Secondly, a web-based questionnaire (Survalyzer) was sent to pharmacists throughout Europe with a home-based therapy programme in place. RESULTS: The patient questionnaire (n = 52) showed that the biopharmaceutical is stored outside the recommended temperature range by 38% of the patients. Additionally, 17% of the patients do not recall getting any information on how to store their biopharmaceuticals, and 23% would like more information on the subject. Furthermore, the questionnaire amongst pharmacists (n = 21) showed that there is a lack of resources and logistical challenges when home-based therapy is applied to biopharmaceuticals used in cancer therapy. CONCLUSION: Home-based therapy with monoclonal antibodies for cancer patients is challenging to implement.

Pilot study of a European oncology regimen reference library and matching algorithm.

OBJECTIVES: As yet, there is no European data standard for naming and describing oncology regimens. To enable real-world cancer treatment data comparisons, the Oncology Data Network created a unified reference database for systemic anti-cancer regimens used in practice across Europe. Data are extracted from clinical systems and mapped to a single standard called the "Core Regimen Reference Library (CRRL)". An automated matching algorithm has been designed based on: drug combinations; administration schedule; and dosing and route of administration. Incomplete matches are flagged for expert review. The aim of this pilot study is to have an expert pharmacist panel test the algorithm's feasibility by comparing computerised and manual matching of regimens that are currently in use in different European countries. METHODS: The combined team pooled a diverse sample of 47 reference regimens used in Europe for solid and haematological cancers. These were then codified to the developed common data standard and the algorithm was used to match them to the CRRL. The expert pharmacist panel from the European Society of Oncology Pharmacy (ESOP) selected 12 regimens from the sample set, ranging from simple to complex, and performed a single-blind test of the algorithm, by systematically matching each original regimen to the CRRL. RESULTS: ESOP validated the algorithm's feasibility based on full concurrence between manual and computer matches thereby validating the algorithm rules and logic with regard to what defines the core characteristics of a regimen and how to compare similarities and differences. CONCLUSIONS: ESOP's validation of the matching algorithm and approach to curating a master library provides confidence in their utility for reliable comparison of real-world regimen usage across Europe.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Safe handling of cytostatic drugs: recommendations from independent science.

OBJECTIVES: Due to their mechanism of action, most classical cytostatic drugs have carcinogenic, mutagenic and/or reprotoxic properties. Therefore, occupational exposure of healthcare staff to these drugs should be prevented. Our objective was to lay out European legislation on this topic and reflect on the process of revising the European CM-directive. We summarise independent European and Dutch studies, and give a concise set of basic recommendations for safe working with cytotoxic drugs in healthcare facilities. METHODS: We were directly involved in the process of revising the CM-directive: first, through an EU commissioned workshop in the Netherlands, and after that by contributing to the pan-European stakeholder symposium. For this aim, we had to gather the relevant study data from the Netherlands and from Europe. We analysed all relevant industry-independent studies and collated a set of basic recommendations. RESULTS: Independent studies show that the development of measures in recent years can lead to a safe work environment. Standardising the cleaning process leads to a significant improvement in environmental contamination in the majority of hospitals. In the Netherlands, exposure of workers was shown to be well beneath the limit value of 0.74 µg cyclophosphamide per week, therefore showing that the measures taken in recent years are adequate. CONCLUSIONS: The safety of healthcare workers is of the utmost importance. Current practice in the Netherlands show that measures taken in recent years are adequate. European legislation should be based on independent scientific research and practice. The first goal should be to bring countries with less safe working levels to a higher level instead of introducing measures that only increase healthcare budgets but not healthcare safety.

Frequency of measuring body weight in (sub)populations of patients with cancer treated with chemotherapy.

OBJECTIVES: Most cytostatics used in cancer treatment are dosed on body surface area (BSA). To administer an appropriate dose it is therefore necessary to know the patient's correct body weight. However, evidence is lacking on how often, after initiation of treatment, body weight should be measured to recalculate BSA. We aimed to assess the relevance of weight measurements during chemotherapy treatment. METHODS: Over a 2 year period we analysed BSA changes in adult patients undergoing chemotherapy treatment. The frequency of and median time to ≥10% BSA change was determined. We assumed a 10% BSA change required dose adjustment and was therefore clinically relevant. RESULTS: Using a database query, data from 2276 patients were used for descriptive statistics, life table analyses and generalised estimating equations. The frequency of ≥10% BSA change occurred in a maximum of 7.6% of the patients, depending on the tumour type. Descriptive statistics in the indications with more than 100 patients showed that BSA changes of ≥10% occurred after 84 days. The groups with the earliest BSA changes were patients with acute leukaemia, lymphoma and pancreatic cancer. CONCLUSIONS: Our observations from real-world data indicate it is safe to omit the current requirement for monthly weight measurements. We advise that during chemotherapy, measuring the body weight in patients who have acute leukaemia, lymphoma or pancreatic cancer or who are under 20 years of age, should be performed at least every 3 months. For other patients, extending this period to a 6-monthly weight measurement should be considered.

Severe Tissue Necrosis after Low-Concentration Cisplatin Extravasation: A Case Report and Review of Expert Guidelines and Literature.

A 65-year-old man was treated with a course of rituximab, cisplatin, and cytarabine. During the second cycle, a volume of 40-50 mL of 0.3 mg/mL cisplatin was extravasated. The patient was treated with a cold pack multiple times a day and cutaneous application of dimethyl sulfoxide cream three times a day for a week. In the months after the extravasation, the patient suffered from worsened swelling and redness and a black crust had formed on the wound. The patient was diagnosed with chemical phlebitis. After watchful waiting for 3 months, antibiotic therapy was started. After 7 months, the wound had healed. On the contrary to what is described in our case, no extravasation guideline classifies cisplatin in a concentration lower than 0.4 mg/ml as a vesicant. The different guidelines also present conflicting recommendations on how to treat the extravasation of cisplatin. In three previous case reports, severe effects of cisplatin extravasation after infusion at low concentration were described as well. We recommend that the findings from our case report are incorporated into extravasation guidelines to ensure optimal treatment of cisplatin extravasations.

Deprescribing in palliative patients with cancer: a concise review of tools and guidelines.

PURPOSE: Palliative cancer patients can benefit from deprescribing of potentially inappropriate medications (PIMs). Tools and guidelines developed for the geriatric population are mainly available. This systematic review gives an overview of available guidelines and tools to deprescribe for palliative cancer patients. METHODS: A systematic search was carried out using the databases SCOPUS and PubMed. Studies focused on palliative cancer patients were included. RESULTS: The search identified 137 studies of which 15 studies were included in this systematic review. Six of the included tools were developed specifically for cancer patients. One of these tools was externally validated and applied in several studies and settings. Guidelines or tools that were not specifically developed for cancer patients but that were applied on cohorts of palliative cancer patients were also included. CONCLUSION: Tools developed for geriatric patients contain drugs that are not inappropriate when used in the palliative cancer care setting. Tools developed for cancer patients are more suitable and can be applied in combination with stepwise methods to individualize deprescribing per patient. The tools and guidelines described in this systematic review can be used to further implement deprescribing in the clinical routine for palliative cancer patients.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC): Pancreatic Cancer.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care throughout the patient journey. Pancreatic cancer is an increasing cause of cancer mortality and has wide variation in treatment and care in Europe. It is a major healthcare burden and has complex diagnosis and treatment challenges. Care must be carried out only in pancreatic cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals detailed here. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

Assessment of occupational exposure to nebulized isopropyl alcohol as disinfectant during aseptic compounding of parenteral cytotoxic drugs in cleanrooms.

Pharmacy technicians are exposed to volatile organic compounds, like the disinfectant isopropyl alcohol (IPA), during the process of aseptic compounding of parenteral cytotoxic drugs. The occupational exposure to nebulized IPA during aseptic compounding has not been investigated. The aim of this study was to investigate the exposure to IPA during aseptic compounding of parenteral cytotoxic drugs and to assess compliance with legal and regulatory limits. As a secondary endpoint, the difference between two disinfection methods was compared regarding the exposure to IPA. The exposure to IPA was measured during five working shifts of 8 hr and one shift of 4 hr. The concentration IPA was measured by using a six-gas monitor. Total daily exposure was calculated as 8-hr Time Weighted Average (TWA) air concentration in mg/m3 and compared with an Occupational Exposure Limit (OEL) value of 500 mg/m3 and incidental peak exposure of 5,000 mg/m3. To assess whether the 8-hr TWA air concentration meets the legal and regulatory limits the Similar Exposure Groups (SEG) compliance test was used. A paired sample t-test was conducted to assess difference in exposure between two disinfection methods. The average 8-hr TWA exposure to IPA during the six measurements varied from 2.6 mg/m3 to 43.9 mg/m3 and the highest momentary concentration measured was 860 mg/m3. The result of the SEG compliance test was 3.392 (Ur value) and was greater than the Ut value of 2.187 which means the exposure to IPA is in compliance with the OEL value. No significant difference in exposure was shown between two disinfection methods (p = 0.49). In conclusion, exposure to IPA during aseptic compounding of parenteral cytotoxic drugs showed compliance to the OEL values with no significant difference in exposure between two disinfection methods.

Identifying options for oncology therapy regimen codification to improve standardization-combined results of an expert panel and a review.

WHAT IS KNOWN AND OBJECTIVE: Chemotherapy drugs are often administered in combinations with predefined interdependent doses and cycle intervals. As yet, there is no global standardization system to describe these complex regimens in a universally comprehensive manner. The aim of this review is to identify which efforts for standardization have been undertaken and which recommendations for databases and nomenclature of chemotherapy regimens are available. METHODS: A literature review was performed to identify all peer-reviewed full-text articles about oncology therapy regimen codification. In addition, the results of this search were evaluated and consensus recommendations from a European expert panel were subsequently added. RESULTS: This review gives an overview of attempts to standardize chemotherapy nomenclature described in the literature, as well as of previously published identified gaps in regimen codification. In addition, we summarized the suggestions for improvement of chemotherapy codification found in the available literature, combining them with the expertise from a European expert panel of oncology pharmacists. WHAT IS NEW AND CONCLUSIONS: We believe that one of the most important error-prevention measures is standardization. However, there is a paucity of data how it may be achieved. Currently available data suggest that standardization has a positive impact on usability for data networks, prescription software, safety and the measurement of the quality of cancer care delivery. Standardization is also a strong pre-requisite for all discussions including oncology pharmacists and oncologists when evaluating chemotherapy regimen in countries in Europe but also all over the world. The recommendations compiled in this review can help to support overdue standardization efforts in this important therapeutic area.

Occupational exposure of pharmacy technicians and cleaning staff to cytotoxic drugs in Dutch hospitals.

Many studies into surface contamination of hospital environments have demonstrated that occupational exposure to cytotoxics through the dermal route remains a possible risk. In this study, we assess the actual dermal exposure of the hands of pharmacy technicians and cleaning personnel in a panel of hospitals performing tasks that pose a risk of exposure. We compare the dermal exposure to a tentative limit value for cyclophosphamide. Pharmacy technicians and cleaning personnel were asked for hand rinsing after performance of nine tasks previously identified as posing a risk of occupational exposure. All samples were analyzed for the presence and quantity of eight antineoplastic drugs. By using data on both the frequency of the performance of the tasks and the measured dermal contamination during these tasks, weekly exposure to the marker drug (cyclophosphamide) was calculated. In five Dutch hospitals, 70 hand rinse samples and 8 blanks were collected. These were analyzed and results were used to calculate weekly exposure. The tentative limit value used was 0.74 µg of cyclophosphamide. For cleaning personnel, all results remained below this threshold value. For pharmacy technicians, the compounding itself also remained well below the limit; however, the task involving preparatory work, as well as the checking of compounded drugs, had a 13% chance of exceeding the limit. All of the highest values were found when employees were not wearing gloves on these tasks. Cleaning personnel and pharmacy technicians compounding cytotoxic drugs in our study were sufficiently protected from occupational exposure. In contrast, pharmacy technicians who perform preparatory and finishing tasks (before and after the actual compounding) are not protected enough when they do not wear gloves.

[Usefulness and uselessness of protective measures; achieving sufficient protection to cytotoxic drug exposure]. / Zin en onzin van beschermende maatregelen.

Cytotoxic drugs can be harmful when healthcare workers are exposed to them, because of their carcinogenic, mutagenic and reprotoxic properties. There are many European and national laws and guidelines, plus local protocols that must be complied with, to protect healthcare workers against cytotoxic drugs. In the Netherlands, the current guidelines for hospitals are well structured and have been proven effective. Compliance to these guidelines remains pivotal, and further attempts to improve worker safety should be aimed at established risks, such as contamination on the outside of commercial drug vials. Non-proven and costly extra measures should not be introduced until their effectiveness has been demonstrated through independent research.