Cost effectiveness of using trastuzumab biosimilars compared to trastuzumab original drugs to treat breast cancer in a hospital setting.

INTRODUCTION: Subcutaneous (SC) drug administration, such as the Herceptin® in an oncology day hospital reduces the administration time of trastuzumab. In the context of combination therapy administration, this time-saving may be called into question. The challenge posed by the deployment of much less expensive IV biosimilar forms raises questions about the cost-effectiveness of SC administration. METHODS: Using data from a french Diagnostic Related Groups regarding prescriptions of intravenous Herceptin® (HIV), Herceptin® biosimilar IV (BSIV), and Herceptin® subcutaneous (HSC), we conducted two simulations. This simulation involved replacing all HSC with BSIV in combination therapy administration (Simulation 1) and subsequently substituting IV forms with SC forms only when prescribed as monotherapy (Simulation 2). A cost-benefit analysis was conducted based on these two simulations, from the hospital's perspective, for Normandy's population over a 1-year timeframe. RESULTS: In Simulation 1, there was an average cost-saving of €12 per patient per year, but it resulted in a loss of 10140 min, equivalent to 10 min per patient per year when compared to the current situation. Simulation 2 yielded average cost-savings for the hospital amounting to €51 per patient per year, along with a time-saving of 67 min per patient per year compared to the current situation. CONCLUSIONS: The development of a program aimed at optimizing the prescription of Trastuzumab holds the potential to deliver significant cost-savings to hospitals while enhancing the quality of service provided to the patients. This optimization involves using H SC in monotherapy and BS IV in combination therapy administration.

Cancer, immune suppression and Coronavirus Disease-19 (COVID-19): Need to manage drug safety (French Society for Oncology Pharmacy [SFPO] guidelines).

The Coronavirus disease (COVID-19) pandemic is disrupting our health environment. As expected, studies highlighted the great susceptibility of cancer patients to COVID-19 and more severe complications, leading oncologists to deeply rethink patient cancer care. This review is dedicated to the optimization of care pathways and therapeutics in cancer patients during the pandemic and aims to discuss successive issues. First we focused on the international guidelines proposing adjustments and alternative options to cancer care in order to limit hospital admission and cytopenic treatment in cancer patients, most of whom are immunocompromised. In addition cancer patients are prone to polypharmacy, enhancing the risk of drug-related problems as adverse events and drug-drug interactions. Due to increased risk in case of COVID-19, we reported a comprehensive review of all the drug-related problems between COVID-19 and antineoplastics. Moreover, in the absence of approved drug against COVID-19, infected patients may be included in clinical trials evaluating new drugs with a lack of knowledge, particularly in cancer patients. Focusing on the several experimental drugs currently being evaluated, we set up an original data board helping oncologists and pharmacists to identify promptly drug-related problems between antineoplastics and experimental drugs. Finally additional and concrete recommendations are provided, supporting oncologists and pharmacists in their efforts to manage cancer patients and to optimize their treatments in this new era related to COVID-19.

Physicochemical stability of oxycodone-ketamine solutions in polypropylene syringe and polyvinyl chloride bag for patient-controlled analgesia use.

OBJECTIVES: The study evaluated the stability of three combinations of oxycodone and ketamine diluted in normal saline (NS) after storage for 7 days at 23°C and exposed to light. METHODS: The stability of three mixtures of oxycodone and ketamine (oxycodone 0.4 mg/mL+ketamine 40 mg/mL, oxycodone 10 mg/mL+ketamine 0.1 mg/mL and oxycodone 10 mg/mL+ketamine 40 mg/mL) in NS stored in a polypropylene syringe and a polyvinyl chloride (PVC) bag was studied. The physical characteristics, including pH, colour and precipitation, were evaluated. The samples were analysed in triplicate by a stability-indicating high-performance liquid chromatography method. RESULTS: There was no significant change in the pH values of any solution. No precipitation or change in colour was observed. All formulations maintained more than 95% of the initial concentration of each drug on day 7. No trace of degradation products was detected. CONCLUSIONS: Ketamine (0.1-40 mg/mL) combined with oxycodone (0.4-10 mg/mL) is physically compatible and chemically stable for 7 days when diluted with NS, packaged in polypropylene syringe or PVC bag and stored at 23°C.

[Pharmacist involvement in supporting care in patients receiving oral anticancer therapies: A situation report in French cancer centers]. / Implication du pharmacien dans l'accompagnement des patients sous anticancéreux oraux : état des lieux dans les centres de lutte contre le cancer (CLCC).

INTRODUCTION: The increasing prescription of oral anticancer therapies has significantly changed inpatient care to outpatient care. This transformation requires an excellent coordination between different professionals to ensure healthcare channel security. METHOD: We performed a prospective study in 18 French cancer centers from March to April 2016. The aim of this study was to identify resources deployed to support patients receiving oral anticancer therapies and to assess pharmacist's involvement. RESULTS: More than half of the centers have developed patient education program and/or practice pharmaceutical consultations. In total, 54.5% have deployed an oral anticancer drugs program and the pharmacist is involved in multidisciplinary teams. In total, 44.4% of the centers have developed hospital-to-community coordination actions but all of them highlight the time-consuming character of those programs. DISCUSSION: Administrative burdens are seriously hindering patient education program's development. Multidisciplinary consultations can offer an attractive alternative because of easy implementation modalities. Finally, hospital-to-community coordination actions seem hard to implement and require harmonization of communication practices, and need more technical and financial means.

Impact of recommendations on crushing medications in geriatrics: from prescription to administration.

The practice of crushing drugs is very common in geriatric units. In 2009 a first study, performed in all geriatric units of a university hospital, showed that numerous errors were made during prescription, preparation and administration. The aim of this second prospective study was to assess the impact of regional and national recommendations in the same geriatric units. A survey of 719 patients (85.3 ± 6.7 years) was performed in 2013. For each patient who received crushed drugs, we recorded the reason the drugs were crushed, pharmacological classes, galenic presentations and the technique used for preparation and administration. Results were compared to the previous study. The number of patients receiving drugs after crushing was significantly lower than in the previous study (22.9% vs. 32.3%, P < 0.001). The number of crushed drugs was lower too (594 per 165 patients vs. 966 per 224 patients (P < 0.01). The main indication for crushing drugs remained swallowing disorders. The dosage form prevented crushing in 24.9% of drugs (vs. 42.0% in 2009, P < 0.001), but the drugs generally remained crushed all together. A mortar was used less often (38.6% vs. 92.6%, P < 0.001), with preference for individual-specific cups (56.1%). Mortars were more often cleaned between each patient (56.0% vs. 11.6%). The vehicle was more often neutral (water 88.5% vs. 5.7%, P < 0.001). This second study shows that regional and national recommendations have led to an overall improvement of practices for crushing drugs. Technical improvements are still possible, in association with appropriate pharmacological studies.

Preliminary validation of self-assessment tool to measure imatinib adherence in patients with chronic myeloid leukemia.

STUDY OBJECTIVES: To develop and validate a self-assessment adherence tool for imatinib in patients with chronic myeloid leukemia (CML), and to correlate the use of this tool with response to treatment and adverse effects. DESIGN: Retrospective cohort study. SETTING: Regional cancer center in France. PATIENTS: Forty-six patients with chronic phase CML treated with imatinib for 6 months or longer as of July 1, 2009. MEASUREMENTS AND MAIN RESULTS: We developed a self-assessment questionnaire consisting of 10 questions to identify patients who were nonadherent to their cancer treatment. Each answer was worth 1 point, resulting in a possible maximum score of 10. The questionnaire was validated in patients receiving imatinib, using an objective adherence evaluation: a patient's score on the self-assessment questionnaire was correlated with prescription refills, expressed as a medication possession ratio. A score of less than 8 was associated with a positive predictive value of 0.83 to have a medication possession ratio below 90%. With use of this questionnaire, half of the patients receiving imatinib would be identified as being nonadherent (sensitivity 0.5). Few adherent patients would be falsely identified as nonadherent, as the questionnaire's specificity was 0.97. CONCLUSION: This self-assessment questionnaire was validated for the first time in patients receiving imatinib for CML treatment. It provides a simple practical tool for health care professionals to assess patient adherence during their routine clinical practice and to propose targeted interventions for those identified as possibly nonadherent.

Knowledge assessment and information needs of oncology nurses regarding inpatient medication.

Although several studies have evaluated the frequency and consequences of medication errors, few have explored their causes. In particular, nurses' knowledge regarding medications has been evaluated minimally. This survey was conducted to determine how nurses master medications prescribed to their patients to determine problems nurses may have with prescribed drugs and identify possible support tools. A questionnaire was created and presented to nurses in a French cancer center. A majority of the respondents correctly identified pharmaceutical classes and medications, as well as administration and storage conditions. However, side effects, contraindications, and drug-drug interactions were not adequately identified. Nurses reported facing problems mainly related to drug administration, drug storage, and generic drugs and their therapeutic equivalence. Multiple tools are in development to help nurses in these areas. This collaborative study between pharmacy and care wards identifies some difficulties nurses have regarding drugs and will help to establish improvement measures within the hospital.

Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel.

Although there has been a significant increase in the availability and use of oral chemotherapeutic agents, the guidelines around their safe handling are still evolving. Although oral chemotherapy is associated with ease of administration, it has the same exposure risks to health care practitioners, patients, and their caregivers as intravenous formulations, and because it is administered in the home, to the families of patients. However, the general misconception appears to be that exposure risk is low and therefore oral chemotherapeutic agents present little risk and are safer to handle. In a series of three roundtable meetings, a team of international pharmacists from North America and Europe reviewed existing guidelines and identified gaps in recommendations that we believe are important for safe handling. The present article is a compilation of these gaps, especially applicable to manufacturers and distributors, storage and handling, and patient education regarding safe handling. These recommendations, on the basis of our experience and of best practices, provide an international perspective and can be adapted by institutions and practices for development of standardized procedures specific to their needs for the safe handling of oral chemotherapeutic agents.

Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care.

Antineoplastic drugs used in the treatment of cancers present with variable renal tolerance profiles. Among drugs with a potential for renal toxicity, platinum salts, and especially cisplatin is a well-known agent that may induce acute and chronic renal failure. The mechanisms of its renal toxicity and the means of its prevention are presented in this article which represent the Clinical Recommendation from the Special Interest Group on Cancer Care of the European Society of Clinical Pharmacy (ESCP).

Uncoupling of oxidative phosphorylation and Smac/DIABLO release are not sufficient to account for induction of apoptosis by sulindac sulfide in human colorectal cancer cells.

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown chemopreventive properties in colorectal cancer, involving both cyclooxygenase (COX)-dependent and -independent mechanisms. Apart from their selectivity for COX isoenzymes, NSAIDs differ in their acidic character which supports ability to uncouple oxidative phosphorylation. To assess the possible contribution of uncoupling to their antineoplastic properties, we compared the effect of sulindac sulfide (SS), an acidic NSAID and NS-398, a non-acidic tricyclic, on mitochondrial function and apoptosis in colorectal cancer cell lines (HT29, Caco-2, HCT15 and HCT116). Although cell lines displayed a different COX status, SS and NS-398 caused growth arrest in a dose-related manner. High dose (10(-4)M) of SS but not of NS-398, increased the percentage of subG1 cell population while reducing mitochondrial transmembrane potential (DeltaPsim). Cyclosporin A (CsA, 1 microM) prevented collapse of DeltaPsim induced by 10(-4)M SS but not by 7.5 microM FCCP used as a protonophoric control. SS and FCCP increased the cytosolic release of Smac/DIABLO which was differently affected by CsA pretreatment depending on the uncoupler. Finally, 7.5 microM FCCP failed to induce apoptosis whereas CsA prevented apoptosis induced by SS from 16% in HCT15 to 41% in HCT116. The present study shows that despite the ability of sulindac sulfide to behave as a protonophoric uncoupler, CsA-sensitive opening of mitochondrial permeability transition pore contributes little to its pro-apoptotic effect in colorectal cancer cells.

[Pharmacology and classification of cyclooxygenase inhibitors]. / Pharmacologie et classification des inhibiteurs de la cyclooxygénase.

The discovery of at least two cyclooxygenase (COX) isoenzymes had two major consequences: i) to give a new impetus to the research on lipid metabolism, giving rise to the crystallization of these peculiar membrane enzymes, the characterization of their active sites and their gene regulation, and the identification of new metabolic pathways; ii) the development of new NSAIDs aimed to have an improved safety profile, the coxibs. These drugs are defined by their COX-2 selectivity which is supported by a negligible inhibitory potency on platelet COX-1 in vitro and ex vivo after oral intake of maximal therapeutic doses. However, the coxibs marketed in France (celecoxib, rofecoxib, parecoxib) are not equivalent in terms of selectivity and some drugs developed by pharmaceutical companies (etoricoxib, lumiracoxib) will be even more selective for COX-2. These "new" coxibs are the final step in the theory of COX-2 selectivity and they will probably be helpful to better define the limitations of the therapeutic concept based on a selective inhibition of this iso-enzyme.

[Standards, options and recommendations for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy-update 2003]. / Recommandations pour la pratique clinique: Standards, Options et Recommandations 2003 pour l'utilisation de l'érythropoïétine recombinante (époetine alfa et bêta, darbepoetine alfa, EPO) dans la prise en charge de l'anémie en cancérologie pour les patients traités par radiothérapie, mise à jour.

CONTEXT: "The Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the twenty French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy. METHODS: The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomised clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002. RESULTS: There is no standard attitude for use of rHuEPO in patients undergoing radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT cancer receiving radiotherapy alone. In patients undergoing curative radiotherapy, it is recommended to correct anaemia under I Og/dL using transfusion rather than rHuEPO. When the haemoglobin concentration is between 12g/dL and 14g/dL initial use of rHuEPO can be an option under certain conditions for radiochemotherapy if the risk of anaemia is high with the chemotherapy regimen used. Anaemic patients should be included in clinical trials to clarify the impact of rHuEPO in terms of local control of the tumour and survival.

[Summary version of the Standards, Options and Recommendations for the use of recombinant erythropoietin (epoietin-alpha and beta, darbepoietin-alpha, EPO) in the management of anaemia in oncology - Update 2003]. / Recommandations pour la pratique clinique: standards, Options et Recommandations 2003 pour l'utilisation de l'érythropoïétine recombinante (époetine alfa et bêta, darbepoetine alfa, EPO) dans la prise en charge de l'anémie en cancérologie, mise à jour (rapport abrégé).

UNLABELLED: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology. To define, on the basis of the critical appraisal of the best available evidence and expert agreement, the clinical situations in which the administration of rHuEPO is indicated, and those in which it is not indicated, except in the setting of randomised controlled trial. METHODS: The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomised clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002. RESULTS: A total of 36 new references, corresponding to 30 randomised clinical trials, were identified. The role of rHuEPO is certain when the haemoglobin concentration is below 10 g/dL, but remains uncertain when the concentration is between 10 g/dL and 12 g/dL. When the haemoglobin concentration is between 12 g/dL and 14 g/dL there is no justification to use rHuEPO to prevent anaemia, except in the setting of autologous blood transfusion programmes before major surgery. No anti-anaemic treatment is justified if the haemoglobin concentration is higher than 14 g/dL, except in the setting of a randomised clinical trial.