Avoiding chemotherapy prescribing errors: Analysis and innovative strategies.

BACKGROUND: At Freiburg University Medical Center, chemotherapy prescriptions are processed via a computerized physician order entry (CPOE) tool and clinically checked by a designated chemotherapy surveillance team. Any error detected is reported instantly, corrected, and prospectively recorded. The objective of the current study was to gain insight into the causes, potential consequences, and future preventability of chemotherapy prescribing errors. METHODS: A detailed analysis of 18,823 consecutive antineoplastic orders placed in 2013 through 2014 was performed. In cooperation with information technology (IT) specialists, the intercepted errors were analyzed for effective future prevention using IT measures. Potential error consequences were determined by case discussions between pharmacists and physicians. RESULTS: Within 24 months, a total of 406 chemotherapy prescribing errors were intercepted that affected 375 (2%) of the total orders. Errors were classified as clinically relevant in 279 of the chemotherapy orders (1.5%). In these cases, reduced therapeutic efficacy (0.44%), the need for increased monitoring (0.48%), prolonged hospital stay (0.55%), and fatality (0.02%) were avoided as potential consequences. The most efficient conventional measures for error prevention comprised checking the order history and patient's medical record, and a detailed knowledge of chemotherapy protocols. Of all the errors analyzed, 61% would be avoided through further software development. The improvements identified are implemented through a validated next-generation CPOE tool. CONCLUSIONS: The upgraded CPOE tool can be shared across other hospitals to raise safety standards and spread potential benefits across a wider patient population. The current analysis also highlighted that approximately 30% to 40% of errors cannot be avoided electronically. Therefore, pharmacovigilance initiatives remain indispensable.

Pomalidomide.

Pomalidomide (originally CC-4047 or 3-amino-thalidomide) is a derivative of thalidomide that is antiangiogenic and also acts as immunomodulatory. Pomalidomide, the recent immunomodulatory agent (IMiD), has shown substantial in vitro antiproliferative and proapoptotic effects. In vivo studies have suggested limited cross-resistance between lenalidomide and pomalidomide. Moreover, pomalidomide achieved very convincing responses in relapsed and refractory multiple myeloma (RRMM) patients, including those, who are refractory to both lenalidomide and bortezomib. Since pomalidomide plus low-dose dexamethasone has shown better responses, progression-free survival (PFS) and overall survival (OS) than high-dose dexamethasone or pomalidomide alone, subsequent trials have pursued or are still investigating pomalidomide triplet combinations, using cyclophosphamide or other novel agents, such as proteasome inhibitors (PI: bortezomib, carfilzomib) or antibodies, like elotuzumab or daratumumab. Pomalidomide has also been assessed in AL amyloidosis, MPNs (myelofibrosis [MF]), Waldenstrom's macroglobulinemia, solid tumors (sarcoma, lung cancer), or HIV, and-for AL amyloidosis and MF-has already been proven to be remarkably active. Due to its potency, pomalidomide was approved for RRMM by the US Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) in 2013 and for drug combination with low-dose dexamethasone in 2015. In June 2017, the FDA further expanded approval for pomalidomide in combination with daratumumab and low-dose dexamethasone for patients with RRMM.

Carfilzomib.

Carfilzomib (CFZ) is a potent, second-generation proteasome inhibitor (PI), with significant activity as a single agent and in combination with other antimyeloma agents in patients with relapsed or refractory multiple myeloma (RRMM). CFZ binds selectively and irreversibly to its target and leads to antiproliferative and proapoptotic effects on cancer cells. This irreversible inhibition is dose- and time-dependent in vitro and in vivo. CFZ as monotherapy and in combination with other antimyeloma agents (e.g., as CFZ and dexamethasone [Kd]) achieved very good responses, progression-free survival (PFS) and overall survival (OS). In several ongoing studies, CFZ is being investigated in triplet and quadruplet schedules of CFZ, lenalidomide and dexamethasone (KRd), CFZ, cyclophosphamide, dexamethasone (KCd) and with antibodies, like elotuzumab or daratumumab. The multitude of completed and ongoing studies confirmed a tolerable safety profile of CFZ, a significantly lower incidence of neuropathy compared to bortezomib (BTZ) and a slightly higher incidence of cardiotoxicity, which is closely observed and precautions taken to avoid them as best as possible. In July 2012, the US Food and Drug Administration (FDA) approved CFZ as a single agent for RRMM patients with disease progression after two prior therapies, including BTZ and immunomodulatory drugs (IMiDs). The combination of KRd and Kd followed, being approved by both FDA and European Medicines Agency (EMA) in 2015 and 2016, respectively. Moreover, CFZ is being evaluated in patients with newly diagnosed MM (NDMM), in high-risk smoldering MM and for maintenance approaches.

Ruxolitinib.

Ruxolitinib, formerly known as INCB018424 or INC424, is a potent and selective oral inhibitor of Janus kinase (JAK) 1 and JAK2. Ruxolitinib has been approved for the treatment of myelofibrosis (MF) by the US Food and Drug Administration (FDA) in 2011 and by the European Medicines Agency (EMA) in 2012, followed by the approval for the treatment of hydroxyurea (HU)-resistant or -intolerant polycythemia vera (PV) in 2014. Both MF and PV are myeloproliferative neoplasms (MPNs) which are characterized by the aberrant activation of the JAK-STAT pathway. Clinically, MF features bone marrow fibrosis, splenomegaly, abnormal blood counts, and poor quality-of-life through associated symptoms. PV is characterized by the overproduction of primarily red blood cells (RBC), risk of thrombotic complications, and development of secondary MF. Ruxolitinib treatment results in a meaningful reduction in spleen size and symptom burden in the majority of MF patients and may also have a favorable effect on survival. In PV, ruxolitinib effectively controls the hematocrit and reduces splenomegaly. Since recently, ruxolitinib is also under investigation for the treatment of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Toxicities of ruxolitinib include myelosuppression, which results in dose-limiting thrombocytopenia and anemia, and viral reactivations. The metabolization of ruxolitinib through CYP3A4 needs to be considered particularly if co-administered with potent CYP3A4 inhibitors. Several further JAK inhibitors are currently under investigation for MPNs or other immuno-inflammatory diseases.