Subcutaneous versus intravenous bortezomib: efficiency practice variables and patient preferences.

BACKGROUND: Subcutaneous bortezomib is noninferior in efficacy to intravenous bortezomib and is associated with a lower incidence of neuropathy in the treatment of multiple myeloma. However, there are no data assessing the effect of subcutaneous bortezomib administration on practice variables or patient preferences. OBJECTIVE: To quantify the difference in efficiency practice variables and patient preferences regarding subcutaneous versus intravenous bortezomib administration in patients with multiple myeloma. METHODS: This study was divided into 2 parts consisting of mutually exclusive patients: a retrospective efficiency study and a survey study. Patients' medical records were reviewed for efficiency data measures including length of infusion chair time and overall infusion center visit time in patients who received at least 6 doses of bortezomib. Patients who received at least 1 dose each of subcutaneous and intravenous administration were surveyed regarding preference, satisfaction, injection site reactions, and quality of life measures. A database was used to identify eligible patients for each portion of the study. RESULTS: A review of 92 medical records demonstrated a 38% reduction in chair time (143 vs 89 minutes; p < 0.001) and a 27% reduction in infusion center visit time (169 vs 123 minutes; p < 0.001) with subcutaneous versus intravenous administration of bortezomib. Of 47 eligible patients, 60% (28) completed the survey; 68% (19; p = 0.0002) of these patients preferred and were more satisfied with subcutaneous bortezomib administration. The overall incidence of injection site reactions was 39% (11) in the surveyed population and was not significantly different between the 2 preference groups. Limitations of the study include single-center design, small sample size, and nonvalidated survey. CONCLUSIONS: Subcutaneous administration of bortezomib is more time efficient for the patient and institution and is preferred by patients compared to intravenous bortezomib.

Pharmacokinetic-directed high-dose busulfan combined with cyclophosphamide and etoposide results in predictable drug levels and durable long-term survival in lymphoma patients undergoing autologous stem cell transplantation.

The clinical advantage of pharmacokinetic (PK)-directed-based dosing on intravenous (i.v.) versus oral busulfan-related toxicity and survival remains unclear. We performed a retrospective cohort study of sequential cohorts of patients comparing PK-directed oral and i.v. busulfan-based conditioning regimens in lymphoma patients undergoing autologous hematopoietic cell transplantation (ASCT). Patients received oral (n = 95), every 6 hours i.v. (IV16, n = 113), or once-daily i.v. (IV4, n = 86) busulfan, cyclophosphamide, and etoposide. PK-directed dosing was performed to achieve a predefined target area under the curve (AUC) of 20,000 µM-min (range: 18,400-21,600 µM-min). PK-directed dose adjustments markedly reduced the number of patients in the oral group with total AUC higher than the targeted AUC range, and reduced the variations of total AUC values in all patient groups. One hundred-day mortality was 2.1%, 3.6%, and 3.5% for oral, IV16, and IV4 cohorts, respectively. Five-year overall survival (OS) was 57% (95% confidence interval [CI] 45%-66%) and 64% (95% CI 53%-73%) for patients who received oral and i.v. busulfan, respectively. Both multivariable and instrumental variable analyses indicated the route of delivery had no significant impact on OS, whereas refractory disease and age ≥55 were significantly associated with poorer OS. In lymphoma patients undergoing ASCT, PK-directed i.v. or oral busulfan-based conditioning regimens have comparable toxicity and OS.

Reduced-dose rasburicase in the treatment of adults with hyperuricemia associated with malignancy.

Tumor lysis syndrome is a life-threatening complication of chemotherapy for patients with leukemia and large tumors with a high proliferative index, such as Burkitt's lymphoma. The syndrome is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. The standard of care for hyperuricemia consists of hydration with or without alkalinization and administration of allopurinol. When treated in this manner, patients often experience persistent hyperuricemia that lasts several days after the start of antineoplastic therapy; sometimes they develop uric acid nephropathy as a consequence. Rasburicase, a recombinant urate oxidase enzyme, quickly removes large amounts of uric acid from plasma. The drug is approved by the United States Food and Drug Administration for management of elevated plasma uric acid levels in pediatric patients with leukemia, lymphoma, or solid tumor malignancies who are receiving chemotherapy. We undertook a retrospective review of adult patients treated with a single dose of rasburicase 6 mg for hyperuricemia associated with malignancy. Ten patients received one 6-mg dose of rasburicase, and one patient received two 6-mg doses as an adjuvant therapy to normalize uric acid levels. In most of the patients, a single 6-mg dose of rasburicase was effective in correcting uric acid levels in the typical time between diagnosis and start of antineoplastic therapy.