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.

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.

NCCN Task Force Report: Oral chemotherapy.

Oral chemotherapy is emerging as a new option for well-selected patients who can manage potentially complex oral regimens and self-monitor for potential complications. If a choice between oral and parenteral therapy is available, patients may opt for oral chemotherapy because it is more convenient to administer, allows them to avoid multiple office visits, and gives them a sense of control over their own cancer care. Whether these potential advantages are maintained in regimens that combine oral and parenteral drugs is less clear. The use of oral chemotherapeutic agents profoundly affects all aspects of oncology, including creating significant safety and adherence issues, shifting some traditional roles and responsibilities of oncologists, nurses, and pharmacists to patients and caregivers. The financing of chemotherapy is also affected. To address these issues, the NCCN convened a multidisciplinary task force consisting of oncologists, nurses, pharmacists, and payor representatives to discuss the impact of the increasing use of oral chemotherapy.

Extended-dosage-interval regimens of erythropoietic agents in chemotherapy-induced anemia.

PURPOSE: The safety and efficacy of extended-dosage-interval regimens of erythropoiesis-stimulating agents (ESAs) for managing chemotherapy-induced anemia (CIA) are reviewed. SUMMARY: Anemia is a frequent complication of chemotherapy. The ESAs epoetin alfa and darbepoetin alfa have been shown to safely and effectively manage CIA; comparable outcomes have been demonstrated between epoetin alfa 40,000 units once weekly and darbepoetin alfa 200 microg every two weeks. These commonly prescribed regimens necessitate extra clinic visits by cancer patients receiving cyclic chemotherapy. ESA administration can now often be synchronized with a three-week chemotherapy cycle because of the recent approval of darbepoetin alfa 500 microg every three weeks for CIA. However, in the Phase III trial providing the basis for this new dosage recommendation, more than 70% of patients required a 40% reduction in the dosage, resulting in an average dose of 375 microg every three weeks. The extended-dosage-interval regimens have not been associated with an increase in cardiovascular or thrombotic adverse events. Extended-dosage-interval regimens of epoetin alfa are under investigation and may provide additional alternatives. Synchronizing ESA therapy with scheduled chemotherapy visits would help minimize disruptions for patients and caregivers and improve the use of health care resources. CONCLUSION: Administration of darbepoetin alfa every three weeks offers the convenience of synchronization of treatment with 21-day-cycle chemotherapy in many patients with CIA. Extended-dosage-interval regimens for epoetin alfa are being investigated and show promise.

Bevacizumab 5 mg/kg can be infused safely over 10 minutes.

PURPOSE: Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor. As a result of concerns for potential infusion-related hypersensitivity reactions (HSRs), initial phase I trials used a 90-, 60-, 30-minute initial infusion sequence. We sought to determine if the initial prolonged infusion was still necessary and if an infusion time of fewer than 30 minutes could be safely used. METHODS: We used computerized pharmacy records to identify all patients who received bevacizumab at our institution in the first 2 years of commercial availability (February 1, 2004, to June 30, 2006). Our institutional adverse drug reaction reporting program was used to identify any infusion reactions possibly related to bevacizumab, and patient medical records were reviewed for confirmation. RESULTS: A total of 1,077 patients were treated with 10,606 doses of bevacizumab, and 765 of these patients received a 5-mg/kg dose (total of 8,494 doses). No HSRs occurred with the 90-, 60-, 30-minute infusion sequence in the first 202 patients. The standard infusion rate was then modified to 30 minutes for all bevacizumab doses. No HSRs were encountered. The infusion was again modified to a rate of 0.5 mg/kg/min. Of the 370 patients who received a total of 2,311 doses of bevacizumab at 5 mg/kg over 10 minutes, six (1.6%) experienced events of minor clinical consequence that were possibly consistent with nonserious HSRs. CONCLUSION: Ninety- and 60-minute initial infusion times are unnecessary. Use of a standard infusion rate of 0.5 mg/kg/min is safe, logical, and the current policy at our institution.

Gemcitabine-induced peripheral edema: report on 15 cases and review of the literature.

Some degree of peripheral edema occurs in up to 20% of patients treated with gemcitabine (Gemzar). The edema is typically mild, requiring discontinuation of the drug in less than 1% of patients. Most patients require no therapy. However, in cases of peripheral edema, grade II or higher, suspension of gemcitabine and treatment with corticosteroids are often necessary, and permanent discontinuation of gemcitabine may be required on occasion. We have identified 15 cases of peripheral edema, grade II or greater, developing in patients receiving gemcitabine chemotherapy at Memorial Sloan-Kettering Cancer Center. The diagnosis was made based on temporal association with drug administration, and exclusion of other potential acute causes of edema including progression of disease and deep vein thrombosis. The 15 patients in this series represent less than 1% of all patients treated with gemcitabine at this institution over the same time period. Gemcitabine was immediately discontinued at the time of the onset of edema in 7 of the 15 patients due to severity of the symptoms. Thirteen of the 15 patients in this case series had experienced peripheral edema previously, and 6 had active low-grade edema at the time the gemcitabine was first administered. Patients receiving gemcitabine should be advised of this potential complication and urged to promptly report its development so that comorbid conditions can be excluded and proper supportive measures initiated. Patients predisposed to peripheral edema from some other cause may be at increased risk for developing severe peripheral edema with gemcitabine.