Recent advances in antiemetics: new formulations of 5HT3-receptor antagonists.

PURPOSE: To discuss new therapeutic strategies for chemotherapy-induced nausea and vomiting (CINV) involving 5-hydroxytryptamine type 3 (5HT3)-receptor antagonists (RAs). SUMMARY: CINV remains poorly controlled in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC); nausea and delayed-phase CINV (24-120 hours after chemotherapy) are the most difficult to control. National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) antiemesis-guideline recommendations for HEC include a four-drug regimen (5HT3 RA, neurokinin 1 [NK1] RA, dexamethasone, and olanzapine). For some MEC regimens, a three-drug regimen (5HT3 RA, NK1 RA, and dexamethasone) is recommended. While 5HT3 RAs have dramatically improved CINV in the acute phase (0-24 hours after chemotherapy), their efficacy declines in the delayed phase. Newer formulations have been developed to extend 5HT3-RA efficacy into the delayed phase. Granisetron extended-release subcutaneous (GERSC), the most recently approved 5HT3 RA, provides slow, controlled release of therapeutic granisetron concentrations for ≥5 days. GERSC is included in the NCCN and ASCO guidelines for MEC and HEC, with NCCN-preferred status for MEC in the absence of an NK1 RA. Efficacy and safety of 5HT3 RAs in the context of guideline-recommended antiemetic therapy are reviewed. CONCLUSION: Recent updates in antiemetic guidelines and the development of newer antiemet-ics should help mitigate CINV, this dreaded side effect of chemotherapy. GERSC, the most recently approved 5HT3-RA formulation, is indicated for use with other antiemetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of MEC and anthracycline-cyclophosphamide combination-chemotherapy regimens.

National survey of comprehensive pharmacy services provided in cancer clinical trials.

PURPOSE: Pharmacy services provided in clinical trials at National Cancer Institute (NCI)-designated centers were assessed. METHODS: This was a cross-sectional survey of 61 NCI-designated cancer centers. Directors of pharmacy were contacted and data were collected electronically via Qualtrics over 2 months. Trial participants were asked to estimate the frequency that their sites performed 26 services and the perceived importance of these services. Services were examined with respect to the difference between their reported performance and their reported importance. Eight of the 26 services showed a difference of at least 40% between the proportion of respondents performing the activities "often" or "almost always" and the proportion considering them "important" or "very important." Demographic information was collected, as well as perceived barriers. RESULTS: Survey response rate was 59% (36 out of 61). The majority of services for clinical trials (19 out of 26) were viewed as important for pharmacists to perform; however, less than half (10 out of 26) were performed more than 50% of the time. Eight services had a gap of more than 40% when comparing the importance versus extent of implementation. Some of the largest gaps were reported in investigator-initiated trials development, medication reconciliation, therapeutic drug monitoring, and oral chemotherapy adherence assessment. Future studies can assist with cost justification by demonstrating the regulatory, safety, and financial benefits of pharmacist involvement in cancer trials. CONCLUSION: A survey of pharmacy directors at cancer centers revealed gaps between what respondents considered important pharmacist services in the provision of cancer clinical trials and the actual performance of those services in their institution.

Stability of extemporaneous erlotinib, lapatinib, and imatinib oral suspensions.

PURPOSE: The stability of extemporaneously prepared erlotinib, lapatinib, and imatinib oral liquid dosage forms using two commercially available vehicles when stored at 4 and 25 °C was evaluated. METHODS: Three batches of extemporaneous oral suspensions were prepared for each drug. Erlotinib and lapatinib tablets were crushed and mixed in a 1:1 mixture of Ora-Plus:Ora-Sweet solution to yield 10- and 50-mg/mL suspensions, respectively. Imatinib tablets were crushed and mixed in Ora-Sweet solution to yield a 40-mg/mL suspension. Suspensions were stored in amber plastic bottles, and samples from each bottle were obtained on days 0, 1, 3, 7, 14, and 28. RESULTS: Erlotinib 10-mg/mL and lapatinib 50-mg/mL oral suspensions in a 1:1 mixture of Ora-Plus and Ora-Sweet retained at least 90% of their initial concentration throughout the 28-day study when stored at 25 °C. Visual inspection revealed notable viscosity changes in the erlotinib and lapatinib suspensions stored at 4 °C for 7 days and beyond. The viscosity of these preparations increased with time and was particularly evident with the erlotinib suspension, which exhibited a puddinglike texture. Imatinib 40-mg/mL oral suspension in Ora-Sweet appeared stable for up to 14 days when stored at both 25 and 4 °C. CONCLUSION: Erlotinib 10-mg/mL and lapatinib 50-mg/mL oral suspensions prepared from commercially available tablets were stable for at least 28 days when prepared in a 1:1 mixture of Ora-Plus:Ora-Sweet at 25 °C. Imatinib 40-mg/mL oral suspension prepared from commercially available tablets was stable for up to 14 days when prepared in Ora-Sweet and stored at 25 and 4 °C.

Physicians as executives: opportunities and strategies for health-system pharmacy leaders.

To deal with the pressures in health care that stress clinical excellence and profitability, health systems are increasingly recruiting physician executives or physicians in leadership and management positions. Physicians occupy less than 5% of all hospital leadership positions, but there is an apparent increase in the recruitment of physician executives. With the growth in the number of physician executives, pharmacy leaders must capitalize on their existing clinical relationship and apply it to health care leadership and management. By focusing on developing an executive presence, by clearly describing a patient-centered strategy and vision for pharmacy, and by nurturing the existing clinical relationships, the pharmacy director can work with physician executives to promote patient-centered pharmacy services.

Formulary Selection Criteria for Biosimilars: Considerations for US Health-System Pharmacists.

Pharmacists will play a key role in evaluating biosimilars for formulary inclusion in the United States. As defined by US law, a biosimilar is a biologic that is highly similar to its reference product, notwithstanding minor differences in clinically inactive components, and should not have clinically meaningful differences from its reference product in safety, purity, and potency. We review biosimilars and the current European Union and US regulatory pathways for biosimilars. Furthermore, we propose a checklist of considerations to ensure that US pharmacists thoroughly evaluate future biosimilars for formulary inclusion. Included in the checklist are considerations related to the availability of preapproval and postapproval safety and efficacy data; differences in product characteristics and immunogenicity between the biosimilar and reference product; manufacturer-related parameters that can affect a reliable supply of quality products; health-system and patient perspectives on product packaging, labeling, storage, and administration; costs and insurance coverage; patient education; interchangeability and differences in the range of indications; and evaluation of institutions' information technology systems.

Assessment of risk evaluation and mitigation strategies in oncology: summary of the oncology risk evaluation and mitigation strategies workshop.

To address oncology community stakeholder concerns regarding implementation of the Risk Evaluation and Mitigation Strategies (REMS) program, ASCO sponsored a workshop to gather REMS experiences from representatives of professional societies, patient organizations, pharmaceutical companies, and the US Food and Drug Administration (FDA). Stakeholder presentations and topical panel discussions addressed REMS program development, implementation processes, and practice experiences, as well as oncology drug safety processes. A draft REMS decision tool prepared by the ASCO REMS Steering Committee was presented for group discussion with facilitated, goal-oriented feedback. THE WORKSHOP IDENTIFIED SEVERAL UNINTENDED CONSEQUENCES RESULTING FROM CURRENT ONCOLOGY REMS: (1) the release of personal health information to drug sponsors as a condition for gaining access to a needed drug; (2) risk information that is not tailored-and therefore not accessible-to all literacy levels; (3) exclusive focus on drug risk, thereby affecting patient-provider treatment discussion; (4) REMS elements that do not consider existing, widely practiced oncology safety standards, professional training, and experience; and (5) administrative burdens that divert the health care team from direct patient care activities and, in some cases, could limit patient access to important therapies. Increased provider and professional society participation should form the basis of ongoing and future REMS standardization discussions with the FDA to work toward overall improvement of risk communication.

Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy.

PURPOSE: Nausea and vomiting are among the most feared complications of chemotherapy reported by patients. The objective of this study was to establish the overall complete response (CR; no emesis or use of rescue medication 0-120 h after chemotherapy) with either ondansetron- or palonosetron-containing antiemetic regimens in patients receiving highly emetogenic chemotherapy (HEC). METHODS: This was a prospective, open-label, randomized, single-center, pilot study that enrolled patients receiving their first cycle of HEC. Patients were randomized to receive either palonosetron 0.25 mg IV (PAD) or ondansetron 24 mg orally (OAD) on day 1 prior to HEC. All patients received oral aprepitant 125 mg on day 1, then 80 mg on days 2 and 3, and oral dexamethasone 12 mg on day 1, then 8 mg on days 2, 3, and 4. Descriptive statistics were used to summarize the data. RESULTS: A total of 40 patients were enrolled, 20 in each arm. All patients were female, and 39 received doxorubicin/cyclophosphamide chemotherapy for breast cancer. For the primary endpoint, 65 % (95 % CI, 40.8-84.6 %) of patients in the PAD arm and 40 % (95 % CI, 19.1-63.9 %) of patients in the OAD arm achieved an overall CR. CONCLUSIONS: While CR rates for aprepitant and dexamethasone plus palonosetron or ondansetron-containing regimens have been published previously, this is the first documentation of CR rates with these regimens in the same patient population. These results may be used to design a larger, adequately powered, prospective study comparing these regimens.

National survey on the effect of oncology drug shortages on cancer care.

PURPOSE: The results of a survey to characterize oncology drug shortages across the United States and the impact of shortages on clinical practice, patient safety, clinical trials, and health care costs are presented. METHODS: A 34-item online survey was distributed to 1672 members of the Hematology/Oncology Pharmacy Association and other organizations to gather information on shortages of oncology drugs (i.e., all drugs essential in the care of cancer patients, including supportive care agents). RESULTS: Two hundred forty-three completed responses, almost all from pharmacists (97%), were analyzed. Delays in chemotherapy administration or changes in treatment regimens due to drug shortages were reported by 93% of survey participants; 85% of respondents reported increased costs, and 10% reported reimbursement challenges related to drug shortages. At 34% of represented institutions, at least 1000 hours of additional labor annually was needed to manage shortages. Changes in therapy leading to near-miss errors were reported by 16% of participants, with 6% reporting one or more actual medication errors attributable to a drug shortage. The oncology medications most frequently reported to be in short supply during the preceding 12 months were fluorouracil, leucovorin, liposomal doxorubicin, and paclitaxel. The conduct of clinical trials was affected by drug shortages at 44% of represented institutions. CONCLUSION: A survey of U.S. oncology pharmacists indicated that oncology drug shortages occurred frequently in the first half of 2011. Shortages led to delays in chemotherapy and changes in therapy, complicated the conduct of clinical research, increased the risks of medication errors and adverse outcomes, and increased medication costs.

Antiemetic control with palonosetron in patients with gastrointestinal cancer receiving a fluoropyrimidine-based regimen in addition to either irinotecan or oxaliplatin: a retrospective study.

BACKGROUND: For moderately emetogenic chemotherapy, palonosetron (PALO) is reported to provide complete control of chemotherapy-induced nausea and vomiting (CINV) in 69% of patients. Prior to August 2009, our gastrointestinal (GI) cancer patients receiving the moderately emetogenic compounds oxaliplatin or irinotecan plus a fluoropyrimidine regimen received ondansetron and dexamethasone orally on day 1 of chemotherapy for CINV prevention. Beginning in August of 2009, ondansetron was replaced by PALO 0.25 mg (intravenous push). METHODS: This is a single-institution retrospective study of GI cancer patients who received oxaliplatin or irinotecan plus a fluoropyrimidine. Failure of an antiemetic regimen was defined as grade ≥1 vomiting or grade ≥2 nausea (Common Terminology Criteria for Adverse Events, version 3) on days 1 through 5 following chemotherapy. Patients were divided for analysis into pre-PALO and post-PALO cohorts. Fisher's exact test compared cohort differences. RESULTS: A total of 305 patients were included in the study, with 157 patients in the pre-PALO cohort and 148 in the post-PALO cohort. For all patients, the risk of antiemetic failure was reduced from 50.3% [95% confidence interval (CI) 42.2-58.4%] to 28.4% (95% CI 21.3-36.4%) with PALO. This reduction in the relative risk of antiemetic failure was observed in all subgroups. CONCLUSION: The addition of PALO may provide increased control of CINV for the moderately emetogenic regimens of oxaliplatin or irinotecan plus a fluoropyrimidine in GI cancer patients.

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.

NCCN Task Force Report: Specialty Pharmacy.

The use of specialty pharmacies is expanding in oncology pharmacy practice. Specialty pharmacies provide a channel for distributing drugs that, from the payor perspective, creates economies of scale and streamlines the delivery of expensive drugs. Proposed goals of specialty pharmacy include optimization of pharmaceutical care outcomes through ensuring appropriate medication use and maximizing adherence, and optimization of economic outcomes through avoiding unwarranted drug expenditure. In oncology practice, specialty pharmacies have become a distribution channel for various agents. The use of a specialty pharmacy, and the addition of the pharmacist from the specialty pharmacy to the health care team, may not only provide benefits for care but also present challenges in oncology practice. The NCCN Specialty Pharmacy Task Force met to identify and examine the impact of specialty pharmacy practice on the care of people with cancer, and to provide recommendations regarding issues discussed. This report provides recommendations within the following categories: education and training of specialty pharmacy practitioners who care for individuals with cancer, coordination of care, and patient safety. Areas for further evaluation are also identified.

Continued challenges with the use of erythropoiesis-stimulating agents in patients with cancer: perspectives and issues on policy-guided health care.

Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.

Perceptions of quality and value in state and local pharmacy professional organizations.

Officer and member perceptions of the quality and value of the services provided by American Society of Health-System Pharmacists (ASHP) state affiliates and local chapters were studied. A survey was mailed in December 2000 to all 249 state society and local-chapter officers in Ohio, Pennsylvania, New York, Minnesota, and Illinois and a random sample of 1191 members. The survey solicited ratings of the quality and value of programs and services related to continuing education, communications, community service, and membership benefits. Of 1440 surveys mailed, 26 were returned as undeliverable; 308 were returned in usable form, for a total response rate of 22%. The most frequent job categories were hospital staff pharmacist (n = 74), hospital pharmacy manager (n = 66), and hospital clinical pharmacist (n = 49). Overall, members perceived lower quality than officers in clinical and administrative continuing-education programs offered by their local chapters. Members also perceived less value in administrative continuing-education programs than did officers. Member and officer perceptions were similar in the areas of communication and community services. Neither members nor officers appeared to value social functions highly as a membership benefit. A survey of state and local affiliates of ASHP in five states identified several areas where officers and members had different perceptions of the quality and value of services provided by these organizations.