Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome.

Rasburicase is a recombinant urate oxidase enzyme administered for treatment of hyperuricemia associated with tumor lysis syndrome. Studies demonstrate effectiveness of single fixed-dose rasburicase as compared to the FDA-approved dose of 0.2 mg/kg intravenously daily for up to five days. Doses in these studies range from 1.5 mg to 7.5 mg. Our study evaluated outcomes in patients who received single 4.5 mg fixed-dose rasburicase. This retrospective, IRB-approved chart review evaluated adult oncology subjects who received fixed-dose rasburicase between January 2007 and April 2014. The primary outcome was percentage of patients with normalization of uric acid (level <8 mg/dL within 24 h) after a single 4.5 mg fixed-dose of rasburicase. Secondary objectives were incidence of initial failure of fixed-dose rasburicase and normalization of uric acid in overweight (body mass index ≥25 kg/m2) versus non-overweight patients. Initial failure was defined as need for additional doses or progression to dialysis within one week of the initial fixed-dose. In the 128 patients included, the mean baseline uric acid level was 14.84 mg/dL. Of the 112 patients with a follow-up uric acid level, 68% achieved normalization within 24 h of rasburicase administration. Thirty-eight patients received additional treatment: 10 received additional dose(s) and 28 underwent dialysis. Normalization of uric acid in overweight versus non-overweight patients was 66% and 73%, respectively. Overall, a single 4.5 mg fixed-dose of rasburicase effectively normalized uric acid in 68% of patients within 24 h. Further studies are needed to determine the optimal single fixed-dose necessary for treatment response across all patients.

Reducing Time to Antibiotic Administration for Febrile Neutropenia in the Emergency Department.

PURPOSE: Febrile neutropenia (FN) is an oncologic emergency, and prolonged time to antibiotic administration (TTA) is associated with increased hospital length of stay (LOS) and worse outcomes. We hypothesized that a febrile neutropenia pathway (FNP) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department (ED). METHODS: This prospective study compared ED FNP patients (> 18 years old), between June 2012 and June 2013 with both historical and direct admissions (DA) cohorts at a multispecialty academic center. Interventions included providing patients with FN-Alert cards, standardizing the definition of FN and recognizing it as a distinct chief complaint, revising ED triage level for FN, creating electronic FN order sets, administering empiric antibiotics before neutrophil count result, and relocating FN antibiotics to the ED. The primary outcome was TTA, with a target goal of 90 minutes after ED presentation. RESULTS: In total, 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts, respectively. Use of the FNP reduced TTA from 235 and 169 minutes in historical and DA cohorts, respectively, to 81 minutes, and from 96 to 68 minutes when the order set was not used versus used in the FNP group (P < .001 for all comparisons). Decrease in hospital LOS was not statistically significant. CONCLUSION: The ED FNP is a significant quality initiative with sustainable interventions, and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED.

Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab.

Febrile neutropenia is a complication of myleotoxic chemotherapy that can markedly decrease quality of life and increase healthcare costs. A granulocyte-colony stimulating factor (G-CSF) is used to increase neutrophil production to reduce the risk of developing febrile neutropenia. However, G-CSF administered on the same day as chemotherapy can worsen and prolong neutropenia. To study and compare the effects of pegfilgrastim on the incidence of febrile neutropenia and grade 4 neutropenia in patients receiving pegfilgrastim on the same day (day 1) versus the next day (day 2 or beyond) of chemotherapy, a retrospective, single-center, nonrandomized, cohort study was carried out of adult non-Hodgkin's lymphoma patients who received pegfilgrastim 6 mg subcutaneously on day 1 or beyond of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with or without rituximab every 3 weeks. Six hundred and fifty-five chemotherapy cycles (320 cycles for the same day and 335 cycles for the next day) were evaluable in 141 patients. Among all cycles, the incidence of febrile neutropenia was 9.4 versus 5.1% in the same-day versus the next-day group (P=0.03). The incidence of febrile neutropenia was the highest after the first cycle in the same-day group, which was 19.4, versus 11.1% for the next-day group (P=0.27). There were three deaths among patients who developed febrile neutropenia, including two in the next-day group versus one in the same-day group. In conclusion, our findings support the need for a randomized phase III study to fully evaluate whether a G-CSF is safer when administered on the next day versus the same day of chemotherapy.

Outcomes in obese and overweight acute myeloid leukemia patients receiving chemotherapy dosed according to actual body weight.

Cytotoxic chemotherapy dosages are traditionally calculated according to body surface area (BSA). No guidelines exist for chemotherapy dosing of acute myeloid leukemia (AML) patients at extremes of weight. We investigated the efficacy and safety of chemotherapy dosed according to BSA based on actual body weight (ABW) among under/normal weight, overweight, and obese AML patients. AML patients (excluding acute promyelocytic leukemia) treated with anthracycline and cytarabine-based remission induction chemotherapy from 2002 to 2009 at Cleveland Clinic were divided into three body mass index (BMI) groups: under/normal weight (BMI ≤ 24.9), overweight (BMI 25.0-29.9), and obese (BMI ≥ 30.0). Among 247 AML patients, 81 (33%) were under/normal weight, 81 (33%) were overweight, and 85 (34%) were obese. Complete remission (CR) rates were similar among these groups (69.1, 79.0, and 76.5%, respectively; P = 0.321), as was median survival (10.7, 16.7, and 14.2 months, respectively, P = 0.352) and 30-day mortality (3.7, 2.5, 7.1%, respectively, P = 0.331). There was no difference among groups in days to neutrophil or platelet recovery, hospitalization days for induction chemotherapy, and bacteremia. After adjustment for confounders (age, sex, BMI, white blood cells, cytogenetic risk, etiology, and bacteremia), overall survival was significantly shorter for normal weight compared to overweight (P = 0.006) and obese (0.038) patients. Response rates and adverse events were not significantly different among AML patients of all weight classes when induction chemotherapy was dosed according to ABW. Induction chemotherapy in these patients can be safely dosed using ABW.