Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment.

BACKGROUND: In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear. OBJECTIVE: The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy. METHODS: This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a "Normal" and a "Delayed" group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups. RESULTS: A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, P = 0.004, and OR = 4.33, P = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, P = 0.006, and AOR = 8.11, P = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment. CONCLUSIONS AND RELEVANCE: Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.

Impact of systemic steroid treatment on talc pleurodesis: a report of six cases.

BACKGROUND: Instillation of sterile graded talc in the pleural space is performed to prevent reaccumulation of malignant pleural effusion after drainage. Talc is thought to encourage pleural adhesions as part of the repair process by provoking inflammation, suggesting that adhesions are less likely to form in patients taking corticosteroids or other drugs with anti-inflammatory effects. However, the relationship between steroid therapy and pleurodesis efficacy remains unclear. CASE PRESENTATION: We report the outcomes of six patients who underwent pleurodesis at Hiroshima University Hospital while being treated with systemic steroid therapy for non-cancer-related illnesses. Talc pleurodesis was successful at the first attempt in five of the six patients. The five successful cases were receiving low-dose oral prednisolone or methyl prednisolone (range, 1-20 mg/day) at the time of pleurodesis and had serum albumin levels ranging from 2.2 to 3.0 g/dL. In contrast, the patient in whom pleurodesis was unsuccessful was receiving a higher dose of prednisolone (40 mg/day) intravenously and had a relatively low serum album level (1.7 g/dL). CONCLUSIONS: The outcome of pleurodesis may be affected by the dose and/or route of systemic steroid therapy. Further analysis with more patients will be necessary to clarify the relationship between steroid dosage and talc pleurodesis success rate.

[Comparison of Pegfilgrastim and Filgrastim for the Primary Prophylactic Effect for Preventing Febrile Neutropenia in Patients Undergoing Rituximab with Dose-adjusted EPOCH Chemotherapy].

The combination of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with rituximab (DA-EPOCH-R) is used for non-Hodgkin lymphoma patients. Febrile neutropenia (FN) is a common complication of treatment with myelo-suppressive chemotherapy, so preventing FN is important for maintaining chemotherapy dosage. Recently, pegfilgrastim has been used as the primary prophylaxis of FN in Japan, but there have been few cases reported using pegfilgrastim for the primary prophylaxis in DA-EPOCH-R. In this study, we retrospectively compared the efficacy of pegfilgrastim with that of filgrastim in patients receiving DA-EPOCH-R in Hiroshima University Hospital. Efficacy assessment was based on incidence of FN and serious neutropenia (neutrophil count <500/µL), hospitalization days and chemotherapy dosage level. Ten patients met the inclusion criteria: pegfilgrastim (n=5, 30 cycles) or filgrastim (n=5, 16 cycles). No difference in efficacy existed between pegfilgrastim and filgrastim in the first cycle; however, 2 of 5 patients in filgrastim group reduced dose level in the total cycles of chemotherapy, no patients in pegfilgrastim group reduced. In conclusion, pegfilgrastim seemed better than filgrastim for the primary prophylaxis in DA-EPOCH-R.

Safety of 90Y-ibritumomab Tiuxetan Treatment for Japanese Patients in Real-world Clinical Practice.

When undergoing 90Y-ibritumomab tiuxetan (90Y-IT) treatment, patients are discharged from hospital soon after initiation of treatment and followed up as outpatients. Thus it is important to apprise patients of the safety information regarding 90Y-IT treatment. However, studies investigating the safety of 90Y-IT in real-world clinical practice are lacking. We sought to investigate the adverse events arising from 90Y-IT administration to patients in our hospital. Patients who received 90Y-IT treatment at Hiroshima University Hospital from April 2010 to December 2014 were eligible for this study. The medical records of the patients were reviewed retrospectively. Eleven patients (median age, 65 years) were enrolled. Patients were classified into 3 groups according to the number of prior regimens: 1, 2-3, or >3, consisting of 5, 4, and 2 patients, respectively. The number of patients with induced grade 3 and 4 hematotoxicity, respectively, was 5 and 0 for leukocytopenia, 3 and 2 for neutropenia, and 3 and 2 for thrombocytopenia. The median nadir time was 37 d for leukocytopenia, 37 d for neutropenia, 36 d for thrombocytopenia, and 43 d for anemia. Patients with 2 or more prior regimens tended to experience grade 3 or 4 hematotoxicity more frequently than those with 1 prior regimen. In conclusion, we showed that hematotoxicity is a major adverse event of 90Y-IT treatment and that the nadir time is later than that with conventional anticancer agents. Medical staff, including pharmacists, should direct attention to the initial symptoms of hematotoxicity, especially in those patients who have received several prior regimens.

[Immunization of pharmacy students in Japan].

We conducted a survey on the immunization requirements of the students in the fourth year of the 4-year-course departments of pharmacy in Japan by using a self-administered questionnaire, which was mailed to the directors of the institutes. Of the 61 departments invited, 54 responded. Program of seroprevalence examination or vaccination was not in place against measles, rubella, mumps and varicella, and hepatitis B in 31.5% (17/54), 53.7% (29/54), 57.4% (31/54), and 68.5% (37/54), respectively. Surveillance of the history of infection and vaccination was carried out in 21 departments, but only 5 departments insisted on documented evidence of immunity. Students who were proven to be susceptible to these diseases were required to receive immunization in most departments that performed seroprevalence examination. Seroprevalence examination was carried out in colleges in 83.3% (25/30), and the expenses were born by department in 70.0% (21/30). On the other hand, vaccination was carried out in colleges in 30.0% (9/30), and the expenses were born by department in 6.7% (2/30). Of the 54 departments, 29, 11, and 3 departments executed these programs in the 3rd year, 4th year, and at the time of admission, respectively. Influenza vaccination during the year of clinical clerkship and tuberculosis skin test was required in 20.4% (11/54) and 37.0% (20/54), respectively; these were carried out in the colleges in 8 and 19 departments and the expenses were born by department in 1 and 18 departments, respectively. Countermeasures against these infectious diseases were found to be insufficient in most departments of pharmacy.