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.

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Background: Evaluating environmental contamination with cytotoxic drugs in hospitals is one of the fundamental requirements to ensure the occupational safety of all healthcare professionals. The European Society of Oncology Pharmacy (ESOP) undertook the first independent, multicenter, pan-European study, involving over a dozen hospitals from 11 different countries, to measure the state of cytotoxic contamination in the workplace. Objective: To obtain an overview of the current situation in European hospitals with regards to cytotoxic drug contamination at various sites, including drug preparation (pharmacy) and administration areas (ward). The secondary objectives are to evaluate the environmental contamination with cytotoxic drugs circulating within a facility known as the hospital medication system (process flow of drug) and to evaluate the impact of changes in local cleaning practices. Materials and methods: The study was carried out at 15 hospitals in Europe evaluating the surface contamination in the preparation and administration areas before (part I) and after (part II and part III) training and the implementation of ESOP cleaning recommendations. Assessment of surface contamination with 11 antineoplastic drugs was performed using wipe samples taken from 10 comparable surfaces (5 each in the preparation and administration areas). These samples were analyzed by liquid chromatography–tandem mass spectrometry. Results: The study demonstrated the presence of surface contamination in preparation and administration areas in all hospitals, with measurable amounts of at least 1 agent detected on sampled surfaces. Before the implementation of the ESOP cleaning recommendations, 324 out of 1595 results were positive (20%). In 11 of 15 hospitals (73%), substances were detected which were not prepared or administrated in the sampling day. After implementation of the ESOP recommendations, only 14% of results were positive (226/1639). Sixty-nine percent of wards (9/13) improved or stayed at the same level in the number of positive samples. The floors on the wards were shown to be the most frequently contaminated (42% of samples were positive). The amount of contamination in the pharmacies was not correlated to the amount of chemotherapy prepared nor to the use of special devices such as closed-system transfer devices. Conclusion: The MASHA study provides an overview of the contamination levels with cytotoxic drugs in European hospitals. Upon implementation of ESOP cleaning recommendations, improvements could be seen, with a reduced number of positive-wipe samples and lower amounts of surface concentration detected. The study demonstrates that improving standard work procedures is able to substantially reduce contamination in the workplace.

O ncology is facing a crisis of affordability that is not sustainable. The economic burden of cancer is growing, as a result of the rising cancer incidence and increased survival, alongside growing investment in disease prevention, diagnosis and treatment. The prices of new cancer drugs continue to increase, placing growing pressure on many healthcare systems. The aim of this article is to explore the reasons why the cost of cancer care is increasing, and why this increase may become unsustainable unless changes are made. There are only limited options for future health spending. Finding ways to improve the allocation of existing resources to achieve the best outcomes for patients will be key to achieving sustainability, whilst safeguarding the continued development of new, effective cancer treatments. Currently, too many cancer drugs are approved without robust evidence of value, and spending more on treatments does not necessarily translate to improvements in health. For all new drugs, in addition to efficacy and safety, there should be a focus on value, with measured outcomes and pricing that ensures these drugs are affordable. Fundamental changes to healthcare systems and industry are needed to sustain cancer care and allow continued access to effective and safe treatments for all patients.

Changes in membrane potential may influence Ca2+-dependent functions through changes in cytosolic free calcium concentration [( Ca2+]i). This study characterized pharmacologically those voltage-dependent Ca2+ channels in normal rat anterior pituitary cells that are involved in the elevation of [Ca2+]i upon high potassium-induced membrane depolarization. The [Ca2+]i was monitored directly by means of the intracellularly trapped fluorescent indicator fura-2. The addition of K+ (6-100 mM) increased [Ca2+]i in a concentration-dependent manner. The fluorescent signal reached a peak within seconds and then decayed to form a new elevated plateau. K+ at the highest concentration used (100 mM) raised [Ca2+]i by about 450 nM. The K+-induced increase in [Ca2+]i was absent in a Ca2+-free medium. BAY K 8644, a 1,4-dihydropyridine Ca2+ channel agonist, also caused an increase in [Ca2+]i. The maximum response in [Ca2+]i upon stimulation with BAY K 8644 (100 nM) was about 40 nM. The half-maximally effective concentration of BAY K 8644 (100 nM) was about 20 nM. The response in [Ca2+]i upon BAY K 8644-stimulation was abolished in a Ca2+-free medium. Predepolarization with various K+ concentrations enhanced the effect of BAY K 8644 (1 microM) on [Ca2+]i. Pretreatment with BAY K 8644 (1 microM) enhanced the response in [Ca2+]i induced by K+ (25 mM). The addition of Mg2+ (30 mM) and nifedipine (1 microM) lowered the resting [Ca2+]i by about 40 and 20 nM, respectively. Mg2+, nifedipine, nimodipine, Gö 5438, verapamil, and diltiazem inhibited the K+ (25 mM)-induced increase in [Ca2+]i; the order of potency (and half-maximally inhibitory concentrations) were nimodipine = Gö 5438 = nifedipine (approximately 100 nM) greater than verapamil (900 nM) greater than diltiazem (greater than 10 microM) greater than Mg2+ (6 mM). Omega-Conotoxin (100 nM) did not inhibit the K+ (25 mM)-induced increase in [Ca2+]i. These data demonstrate that, over a wide range, membrane depolarization induced by high potassium concentration is indeed associated with increases in [Ca2+]i in normal rat anterior pituitary cells. This elevation of [Ca2+]i is mainly due to an influx of Ca2+ through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels (L-type).