Utilization patterns and clinical outcomes of rasburicase administration according to tumor risk stratification.

PURPOSE: Current guidelines for tumor lysis syndrome management recommend rasburicase for high-risk patients. Adherence to guidelines has not been well studied, and the correlation between uric acid reduction and clinically relevant outcomes, such as acute kidney injury, remains unclear. Our study aims to describe rasburicase utilization patterns and outcomes in cancer patients with varying risks for tumor lysis syndrome. METHODS: In this retrospective cohort study, we included cancer inpatients who received rasburicase for tumor lysis syndrome management at two affiliated academic hospitals from 2009 to 2015. Patients were classified by tumor lysis syndrome risk categories prior to drug administration. Primary outcomes included acute kidney injury incidence and renal recovery. Secondary outcomes included uric acid nadir, mortality, and hospital length-of-stay. RESULTS: Among 164 patients, 42 (26%) had high-, 63 (38%) had intermediate-, and 59 (36%) had low-risk for tumor lysis syndrome. A total of 94 patients (57%) had existing renal dysfunction prior to rasburicase use. This occurred more frequently in low- (68%) compared to intermediate- (57%) and high- (43%) risk patients (p = 0.044). A greater proportion of patients in the high-risk group (78%) had renal recovery when compared to the intermediate- (61%) or low- (45%) risk groups (p = 0.056). Despite a similar length of stay, the high-risk group had a significantly lower 30-day mortality (10%) when compared to intermediate- (25%) or low- (32%) risk groups (p = 0.029). CONCLUSIONS: Our results suggest that rasburicase may be frequently prescribed to treat hyperuricemia unrelated to tumor lysis syndrome in cancer patients. Improved education and adherence to guidelines may improve clinical and economic outcomes associated with rasburicase administration.

Clinical utility of routine proteinuria evaluation in treatment decisions of patients receiving bevacizumab for metastatic solid tumors.

BACKGROUND: Bevacizumab is an anti-vascular endothelial growth factor monoclonal antibody approved for use in treatment of patients with metastatic breast, colorectal, and non-small cell lung cancer. In the pivotal Phase 3 clinical trials, grades 3-4 proteinuria occurred in <5% of patients. The manufacturer recommends monitoring for the development of proteinuria but does not provide specific recommendations, except to discontinue treatment if the patient develops nephrotic syndrome. OBJECTIVE: To determine the incidence and severity of elevated proteinuria and the frequency of changes in bevacizumab administration due to elevated proteinuria; secondary objectives included analysis of the cost of routine proteinuria monitoring and the relationship of proteinuria with other patient comorbidities such as diabetes, hypertension, chronic kidney disease, and viral hepatitis. METHODS: A retrospective chart review was performed at the University of Washington Medical Center, a large academic teaching hospital, and its affiliated ambulatory clinics at the Seattle Cancer Care Alliance. Patients treated with bevacizumab and seen in the breast, lung, and gastrointestinal cancer clinics from June 1, 2005, to November 30, 2007, were included in the study. RESULTS: A total of 243 patients were included in the analysis. Only 1.6% of these patients developed grades 3-4 proteinuria. All 4 of these patients had a history of hypertension, 2 of these patients had prior chronic kidney disease, and 3 patients had prior viral hepatitis. Elevated proteinuria affected treatment decisions in 2% of patients. Over $130,000 was charged to patients for monitoring of proteinuria. CONCLUSIONS: These results demonstrate that the development of grades 3-4 proteinuria with bevacizumab is rare and affects treatment decisions in few patients with metastatic solid tumor. Furthermore, routine proteinuria monitoring is associated with high cost and may not be required before each administration.

Musculoskeletal pain associated with corticosteroid therapy in cancer.

Corticosteroids have multiple uses in the care of the cancer patient. Although they confer benefit to the patient, high doses and extended duration of use may lead to significant adverse effects. Adverse effects such as osteoporosis-induced fractures, osteonecrosis, myopathy and myalgias can cause significant pain and have a negative impact on the patient's quality of life. In this paper, I will review the mechanisms involved in the toxicity, risk factors, prevalence, prevention, and treatment strategies.

Comparative effectiveness of rasburicase versus allopurinol for cancer patients with renal dysfunction and hyperuricemia.

While rasburicase has shown efficacy to rapidly correct hyperuricemia compared with allopurinol, its overall impact in improving clinically significant outcomes, such as acute kidney injury (AKI), in tumor lysis syndrome (TLS) is unknown. In this retrospective cohort study, we included all hospitalized cancer patients with hyperuricemia and AKI who received rasburicase +/- allopurinol or allopurinol alone from 2009 to 2015. Inverse probability of treatment weighting using propensity score was used to account for potential confounders and to estimate the causal effect associated with differential drug treatment. 150 patients met inclusion criteria; 89 received rasburicase +/- allopurinol and 61 received allopurinol alone. Weighted outcome regression analysis demonstrated that rasburicase was associated with significantly lower mean uric acid nadir at 7 days compared to allopurinol (2.70 versus 5.82 mg/dL, p < 0.01). However, likelihood of renal function recovery (OR = 0.90, p = 0.79), creatinine nadir by 7 days (1.80 versus 1.66 mg/dL, p = 0.51), and final creatinine by 30 days (2.08 versus 2.07 mg/dL, p = 0.98) did not significantly differ. In conclusion, the clinical benefit of rasburicase in promoting renal function recovery in cancer patietns with concurrent hyperuricemia and renal failure remains inconclusive. Our results suggest that correction of hyperuricemia as a surrogate endpoint may not be associated with significant renal function improvement, particularly if renal dysfunction is unrelated to TLS.

Cancer pain: perspectives of a medical oncologist.

Pain is highly prevalent in cancer patients and primarily managed by medical oncologists. This article reviews cancer pain syndromes related to cancer and sequelae of treatment. We discuss the assessment and treatment of cancer pain with pharmacotherapy and chemotherapy, and the role of pain specialists. There are numerous barriers to care, which arise from both the physician and patient. We review approaches that diminish these barriers to improve treatment of cancer pain.

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.

Current status of cetuximab for the treatment of patients with solid tumors.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical evidence, and safety, as well as the potential directions for use, of the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab. DATA SOURCES: A MEDLINE search (1966-December 2005) was conducted using the following terms: cetuximab, Erbitux, C225, epidermal growth factor receptor, and EGFR. Additional information was obtained via meeting abstracts, bibliographies from relevant articles, national guidelines, and the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Preclinical and clinical trials utilizing cetuximab in the treatment of solid tumors were selected from the data sources. All published, randomized clinical trials involving cetuximab in treatment of metastatic colorectal cancer and studies providing a description of the pharmacology, pharmacokinetics, safety, or efficacy were included in this review. DATA SYNTHESIS: Many solid tumors overexpress EGFR, making it an ideal target for anticancer agents. Cetuximab is the only EGFR monoclonal antibody commercially available and is approved for the treatment of EGFR-expressing, metastatic colorectal cancer in patients refractory or intolerant to irinotecan. Data on patients with other solid tumors are encouraging with cetuximab used as monotherapy or in combination with chemotherapy, radiation, or other targeted agents. Common adverse effects include dermatologic and hypersensitivity reactions. CONCLUSIONS: Further clinical data are necessary to clearly define the role of cetuximab in the treatment of patients with solid malignancies, with emphasis on survival and quality-of-life benefits relative to its cost.