Amy M. Pick

Pazopanib for the treatment of metastatic renal cell carcinoma.

BACKGROUND Renal cell carcinoma (RCC) is the most common cancer in the kidneys. Until 2005, treatment options were limited to immunotherapy. Since that time, there have been numerous targeted therapy agents approved with improved efficacy toward RCC. Pazopanib is a multi-tyrosine kinase inhibitor that was approved by the US Food and Drug Administration in October 2009 and by the European Medicines Agency in June 2010 for the treatment of metastatic RCC. OBJECTIVE The objective of this report was to review pazopanibs mechanism of action; pharmacologic, pharmacokinetic, and dynamic properties; potential drug interactions; and the results of clinical trials evaluating efficacy and tolerability associated with pazopanib for the treatment of RCC. METHODS MEDLINE, International Pharmaceutical Abstracts, and Web of Science were searched for English-only clinical trials and therapeutic reviews (publication dates: 2000-January 1, 2012). Abstracts from the 2000 to 2011 meetings of the American Society of Clinical Oncology were searched for an updated safety profile and tolerability data of pazopanib in RCC. References from relevant articles were reviewed. Key search terms included pazopanib, Votrient, GW786034, renal cell carcinoma, adverse events, pharmacology, pharmacokinetic, and clinical trial. RESULTS Two clinical trials met the inclusion criteria for the use of pazopanib in RCC (a Phase II and a Phase III trial). Pazopanib is an inhibitor of numerous tyrosine kinases, including vascular endothelial growth factor receptor and platelet-derived growth factor receptors. It is involved in inhibiting signaling pathways, angiogenesis, and cell proliferation. Pazopanib was approved by the US Food and Drug Administration and the European Medicines Agency at the dose of 800 mg daily. Peak concentrations are achieved within 2 to 4 hours of this dose with a mean t(½) of 35 hours. The pharmacokinetic properties of pazopanib are affected by food as well as by crushing the tablet. A 2-fold increase in AUC was seen when pazopanib was administered with a high-fat meal as well as when crushing the tablet. Thus, pazopanib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Pazopanib is primarily metabolized by cytochrome P-450 3A4, and caution should be used with concomitant administration of cytochrome P-450 inducers and/or inhibitors. In a Phase III trial of pazopanib in metastatic RCC, pazopanib reportedly improved progression-free survival from a median of 4.2 to 9.2 months compared with placebo (P < 0.0001). The most common adverse effects of pazopanib were hypertension, hair depigmentation, diarrhea, nausea, anorexia, and vomiting. Many of the grade 3/4 toxicities were hepatic in nature, with elevations occurring in aspartate aminotransferase, alanine aminotransferase, and bilirubin. CONCLUSIONS Pazopanib is reportedly effective in the treatment of metastatic RCC. Although there are currently no direct comparisons between pazopanib and other tyrosine kinase inhibitors, the data suggest that pazopanib may be a first-line option in the treatment of RCC. The only Phase III trial of pazopanib suggests improvement of progression-free survival in RCC as well as tolerability in the selected population.

Improving Adherence to Oral Cancer Therapy in Clinical Practice

Adherence to oral chemotherapy regimens maximizes their effectiveness and minimizes any potential toxicities. Factors specifically related to the treatment, patient, and health care provider may influence medication adherence. Treatment‐related factors include the complexity of the regimen, the cost of therapy, the possibility of side effects, and the delay in treatment benefits. Meanwhile, patients may not have an adequate support system or an understanding of the need for the medication, and providers may not fully succeed in communicating the importance of adherence and the types of side effects that may occur. Nonadherence may lead to an increased risk of toxicity, decreased effectiveness, and increased utilization of health care resources. Although various methods for measuring adherence are available, self‐reporting is the most widely used. Studies describing adherence in a broad range of cancers are reviewed. Treatment of chronic myeloid leukemia has been revolutionized by the development of oral tyrosine kinase inhibitors that are highly effective in managing the disease when taken consistently. However, nonadherence is relatively common and can lead to reduced rates of response and increased medical costs. Similar effects of nonadherence on outcome and cost have also been observed in patients with various other hematologic malignancies and solid tumors. Interventions to improve adherence to oral chemotherapy regimens include communication about the importance of adherence and the potential consequences of nonadherence, simplification of the patients medication schedule (if possible), and inclusion of a caregiver or family member in the conversation. Written materials should always be provided to accompany verbal instructions. This review summarizes factors influencing medication adherence, impact of nonadherence on patient outcomes, methods for measuring adherence, previous studies of nonadherence in patients with cancer, common barriers to access, and interventions to improve adherence in the community setting.

Implementation of a safety program for handling hazardous drugs in a community hospital

PURPOSE The implementation of a safety program for handling hazardous drugs in a community hospital is described. SUMMARY A committee of representatives of the departments of pharmacy, nursing, human resources, safety, radiology, performance improvement, employee health, and environmental services and members of the hospital administration was formed to formally address the management of hazardous drugs in a community, not-for-profit, adult hospital in Omaha, Nebraska. Published guidelines and regulations were reviewed to determine the hospitals compliance with the handling of hazardous drugs. A knowledge deficit regarding the risk and severity of occupational exposure to hazardous drugs was identified. A formal education plan was immediately implemented providing inservice education to all staff who may come into contact with hazardous drugs. Each drug was electronically tagged in the hospital computer system. The nitrile gloves used in the pharmacy were switched to a brand tested for resistance to chemotherapy drug permeation. The use of personal protective equipment for all health care workers who may come into contact with hazardous drugs was also instituted. Waste stream management was addressed, and a new waste stream was identifed and implemented to address chemicals regulated by the Resource Conservation Recovery Act. Nursing, pharmacy, and housekeeping personnel were extensively educated on the different waste streams and the importance of segregating waste at the point of use. All gloves for housekeeping and laundry service staff were replaced with hazardous-drug-rated nitrile gloves. CONCLUSION A gap analysis allowed a multidisciplinary team to establish a safety program for managing hazardous drugs in a community hospital.

An Oncology Pharmacy Practice Elective Course for Third-Year Pharmacy Students

Objective. To develop and implement a 1-credit-hour oncology pharmacy practice elective course for third-year pharmacy students and assess its impact on examination scores in a required pharmacotherapeutics course. Design. Major topics were identified to focus on therapeutic management and supportive care of the oncology patient. Psychosocial topics were incorporated to help pharmacy students better relate to oncology patients. Assessment. Learning was assessed by means of 2 computer-based examinations, weekly reflection posts, and a completed oncology service-learning project and reflection paper. Students enrolled in the course achieved higher pharmacotherapeutics oncology section examination scores than students who had not taken the course. Also, this course increased students’ interest in oncology pharmacy. Conclusion. The oncology pharmacy elective course has received overwhelmingly positive feedback from students and student enrollment continues to grow. We will continue to offer this course to future practitioners.

Temozolomide-Induced Desquamative Skin Rash in a Patient with Metastatic Melanoma

Temozolomide is an oral alkylating agent used in the treatment of metastatic melanoma. Commonly reported adverse effects of the drug include nausea and vomiting, constipation, headache, and fatigue, as well as myelosuppression, which may be dose limiting. Few reports have described dermatologic adverse effects such as rash and pruritus, and, to our knowledge, none have discussed the seriousness or extensiveness of the rash. We describe a 37‐year‐old woman who was receiving temozolomide for treatment of metastatic melanoma. After 6 weeks of therapy, the patient developed an unexplained fever. The drug was discontinued, and the fever resolved within 2 days. Temozolomide was restarted 2 months later; the patient again developed a fever. This time the fever was accompanied by a diffuse erythematous skin rash that progressed to an extensive, full‐body, desquamative skin rash. The rash was treated with moisturizing cream along with intravenous and topical corticosteroids and antibiotics. Due to the severity of the rash, temozolomide was permanently discontinued. Even after its discontinuation, the patient experienced the rash on a long‐term basis, with periodic exacerbations. However, none were as severe as the first rash. The patients metastatic disease remained stable for the next 2 years. According to the Naranjo adverse drug reaction probability scale, the likelihood that temozolomide was responsible for the adverse drug reaction of fever was probable (score of 6). Clinicians should be aware that an erythematous and exfoliative rash may be induced by temozolomide, and be familiar with the pharmacologic and supportive measures necessary for its treatment.

Fatal hepatic and renal toxicity as a complication of trabectedin therapy for radiation-induced sarcoma

Trabectedin therapy was prescribed for a patient with radiation-induced sarcoma. Two doses of trabectedin were given before therapy was discontinued with the patient experiencing renal and liver failure. Despite discontinuing trabectedin the patient continued to experience increases in liver transaminases, bilirubin, blood urea nitrogen, and serum creatinine. Hemodialysis was initiated with no improvement. With all other causes being ruled out, trabectedin likely caused hepatic and renal failure leading to death in this patient. Recent literature suggests that patients may benefit from prophylactic dexamethasone as a means of reducing hepatic toxicity.

Identification of biomarkers in pazopanib treated patients with renal cell carcinoma

Targeted therapy has become the mainstay in the treatment of renal cell carcinoma (RCC). That being said, it is difficult to predict which patients will respond to targeted therapy. A recent article published in The Lancet Oncology attempts to identify biomarkers in patients receiving pazopanib that may be helpful in the clinical management of renal cell carcinoma.

Inter-Rater Reliability in the Evaluation of a Thrombosis Risk Assessment Tool

Introduction Venous thromboembolism (VTE) is a health concern that is common among hospitalized patients. There are more than 200,000 new VTE events that occur annually. The majority of VTE cases are asymptomatic, and 70% to 80% of fatal pulmonary embolisms (PE) in the hospital are not predictable. The ENDORSE study evaluated more than 35,000 patients and reported that only 58% of surgical and 39% of medical patients at risk for VTE received American College of Chest Physicians (ACCP) recommended VTE prophylaxis. 1 Nebraska Methodist Hospital evaluated and revised the thrombosis risk assessment tool published by Motykie et al 3 for use with the institutions medical and surgical patients. Objectives The purpose of this study was to assess the reliability of the thrombosis risk assessment tool. Secondary end points were to determine if patients were treated with the appropriate therapy based on their total risk score, to assess if therapy was appropriately adjusted after pharmacist intervention, and to determine the incidence of VTE. Methods Three evaluators completed a thrombosis risk assessment of 100 patients chosen randomly upon hospital admission during a 1-month period. Pearsons correlation coefficients were determined to assess reliability. Patient medication profiles were evaluated for the proper prophylaxis regimen and interventions were made as needed. Quality control provided data on the incidence of thromboembolic events. Results The thrombosis risk assessment tool was shown to have good clinical reliability. Seventy percent of patients were treated appropriately. Interventions were generally accepted after pharmacist intervention unless patients were soon to be discharged. The incidence of deep vein thrombosis in surgical and medical patients and pulmonary embolism in surgical patients was decreased after implementation of the thrombosis risk assessment tool. However, the impact of the thrombosis risk assessment tool on the incidence of pulmonary embolism in the medical patients could not be determined.