Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) are not recommended for venous thromboembolism (VTE) treatment in patients with cancer because their safety and efficacy have not been compared to low molecular weight heparin (LMWH) in large trials. Routine anti-Xa monitoring in cancer patients on LMWH is also not recommended due to limited data correlating anti-Xa levels and outcomes. OBJECTIVE: Compare the safety and efficacy of DOACs to LMWH and warfarin and assess the relationship of anti-Xa monitoring and outcomes in patients with cancer taking LMWH in an urban university setting. METHODS: This retrospective, cohort study analyzed the recurrence of VTE and number of bleeding events in patients with cancer. RESULTS: There were 131 patients included in the analysis. There was no difference seen in the rate of recurrent VTEs between the LMWH, warfarin and DOAC groups (9.3%, 5.9%, 9.1%, p = 0.89). There was also no difference in the rate of bleeding between groups (10.5%, 14.7%, 9.1%, p = 0.576). There was an increased rate of mortality seen in the LMWH group (26.7% vs. 2.9% vs. 18.2%, p = 0.006). There was no difference seen in recurrent VTE (10.3% vs. 8.5%, p = 0.53) or bleeding (10.3% vs. 10.7%, p = 0.661) between the monitored and unmonitored LMWH patients. CONCLUSION: Results of this analysis suggest DOACs may be as safe and effective as LMWH and warfarin for the treatment of VTE in patients with cancer, and there may be no clinical benefit to routine anti-Xa monitoring in patients on LMWH treatment. However, larger studies are needed to confirm these observations.

A prospective study of intravenous pentamidine for PJP prophylaxis in adult patients undergoing intensive chemotherapy or hematopoietic stem cell transplant.

Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is recommended for patients undergoing hematopoietic stem cell transplantation (HSCT) or intensive chemotherapy. Trimethoprim-sulfamethoxazole and inhaled pentamidine are used frequently, but are limited, by their tolerability and therefore compliance. Intravenous (IV) pentamidine is a potential alternative agent. Here we conducted the first prospective study of the safety and efficacy of IV pentamidine for PJP prophylaxis in adult patients undergoing HSCT or intensive chemotherapy (clinicaltrials.gov NCT02669706). Fifty patients requiring PJP prophylaxis were enrolled and received monthly IV pentamidine at 4 mg/kg (maximum 300 mg) while undergoing intensive chemotherapy or HSCT. Patients were followed for the occurrence of PJP pneumonia and for adverse events. Satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM Version 1.4) survey. Seventeen (34%) patients experienced a grade 1 or 2 adverse event. There were no grade 3/4 events. The TSQM questionnaire indicated that the majority of patients were satisfied with the administration of IV pentamidine (n = 43, 86%, p = 0.01). There were no cases of PJP during the 24 month follow-up period. Our study illustrates the safety, feasibility, and high degree of patient satisfaction when using IV pentamidine for PJP prophylaxis.

Pharmacological management of anticancer agent extravasation: A single institutional guideline.

Although the risk of extravasation of a chemotherapy (anticancer) medication is low, the complications associated with these events can have a significant impact on morbidity and health care costs. Institutions that administer anticancer agents should ideally have a current guideline on the proper management of the inadvertent administration of these toxic medications into tissues surrounding blood vessels. It is imperative that the health care team involved in administering drugs used to treat cancer be educated on the risk factors, preventative strategies and treatment of anticancer extravasations, as well as practice safe and proper administration techniques. Anticancer agents are generally divided into classes based on their ability to cause tissue damage. The review of current published guidelines and available literature reveals a lack of consensus on how these medications should be classified. In addition, many recently approved drugs for the treatment of cancer may lack data to support their classification and management of extravasation events. The treatment of the majority of extravasations of anticancer agents involves nonpharmacological measures, potentially in the ambulatory care setting. Antidotes are available for the extravasation of a minority of vesicant agents in order to mitigate tissue damage. Due to the limited data and lack of consensus in published guidelines, a working group was established to put forth an institutional guideline on the management of anticancer extravasations.

The life, death, and attempted rebirth of bevacizumab in breast cancer.

Breast cancer is the leading cause of cancer in women. In recent years, there has been immense drug discovery and development in the field of breast cancer. Most recently, the role of vascular endothelial growth factor has moved to the treatment forefront with bevacizumab immersed into the literature as well as the media. Bevacizumab, a vascular endothelial growth factor inhibitor FDA approved for the treatment of other cancers, was first studied in metastatic breast cancer. Its use in human epidermal growth factor receptor 2-negative metastatic breast cancer ultimately failed to show an improvement in overall survival in landmark trials (E2100, AVADO, RIBBON-1 and RIBBON-2) despite its positive impact on progression-free survival. The role is yet to be determined in triple negative breast cancer as well as in the adjuvant and neoadjuvant settings. Trends begin to emerge as bevacizumab is combined with other chemotherapeutic drugs in terms of toxicities. The addition of bevacizumab is associated with an increase in the dose-limiting toxicities of the drugs combined in the regimen. As previous literature suggest, hypertension and proteinuria were also seen with the addition of bevacizumab, both of which are known adverse events. Lastly, there is a trend towards increased incidence of heart failure when bevacizumab is combined with another cardiotoxic medication, doxorubicin. This toxicity has been shown to be reversible in the majority of the cases and has a low incidence in the currently published literature.

Rasburicase in cancer-related hyperuricemia.

Tumor lysis syndrome (TLS) is an oncological emergency consisting of several metabolic derangements: hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. The rupture of tumor cells in cancer patients can be spontaneous or caused by anticancer therapy. Clinical manifestations of TLS include nausea, anorexia, arrhythmias or renal failure. Prevention and treatment measures include aggressive hydration and concomitant antihyperuricemic therapy. Allopurinol has historically been the only available pharmacological option. Rasburicase was subsequently approved for the management of elevated plasma uric acid levels in adults. This recombinant urate oxidase converts uric acid to allantoin, a more soluble byproduct that is safely eliminated by the kidneys. Manufacturer-labeled dosing for rasburicase in the pediatric and adult populations is 0.2 mg/kg as a daily intravenous (i.v.) infusion for up to 5 days. This review summarizes several studies suggesting that flat, single rasburicase dosing regimens may be just as effective as weight-based dosing. The optimal, most cost-effective adult dose and schedule have yet to be determined.