Good response to methotrexate is associated with a decrease in the gene expression of ABCG2, a drug transporter, in patients with rheumatoid arthritis.

OBJECTIVES: Methotrexate (MTX) is used as an anchor drug in the treatment of rheumatoid arthritis (RA), although more than a half of the patients with RA require additional treatments. We designed a prospective study involving two medical centers in Japan to examine the association between the expression of MTX-related genes including a drug transporter ATP-binding cassette sub-family G member 2 (ABCG2) gene and the clinical response to MTX in MTX-naive patients with RA. METHODS: The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. RESULTS: Based on the clinical response at 12 weeks after the initiation of MTX, 24 patients were classified into good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of the baseline gene expression levels to predict the EULAR good response at week 12 showed a significant association with ABCG2 expression alone. Furthermore, the rate of baseline expression of ABCG2 mRNA above the cut-off value determined using a receiver operating characteristic curve was higher in good responders than in non-good responders (p = .012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median -76% vs. +41% from baseline, respectively; p = .011). The ABCG2 expression level did not correlate with DAS28 at baseline or week 12. CONCLUSIONS: Our study revealed that good response to MTX is associated with a decrease in the expression of ABCG2 in patients with RA.

Surface contamination of the outer and blister packages of oral anticancer drugs: A multicenter study.

INTRODUCTION: All guidelines necessitate wearing personal protective equipment during dispensing of oral anticancer drugs. This study aims to measure the degree of contamination on the press-through-package strips of oral anticancer drugs in Japan. METHOD: Surface contamination of the external packaging of anticancer drugs was examined by performing wipe tests at four hospitals and two community pharmacies. The following commercially available drugs were examined: Xeloda®, TS-1®, and methotrexate tablets and SA-1® and Rheumatrex® capsules. RESULTS: The wipe tests' results revealed that the contamination levels of Xeloda® and TS-1® tablets and SA-1® capsules were within their detection limits. In some facilities, the contamination levels on the press-through-package strips of Rheumatrex® capsules were 3.27 × 10-1, which is close to its detection limit. However, across all facilities, the contamination level of methotrexate tablets was above its detection limit. CONCLUSION: The results of this study suggested that adherence to oral anticancer drugs may not occur during manufacture or transportation. However, it may be due to the presence of pollutants in the facilities. Prevention of pollution in facilities might eliminate the need to wear personal protective equipment during dispensing of oral anticancer drugs.

Salient Features and Outline of the Joint Japanese Guidelines for Safe Handling of Cancer Chemotherapy Drugs.

The purpose of this paper is to introduce the outline and describe the salient features of the "Joint Guidelines for Safe Handling of Cancer Chemotherapy Drugs" (hereinafter, "Guideline"), which were published in July 2015. The purpose of this Guideline is to provide guidance to protect against occupational exposure to hazardous drugs (HDs) to all medical personnel involved in cancer chemotherapy, including physicians, pharmacists, and nurses and home health-care providers. The Guideline was developed according to the Medical Information Network Distribution Service guidance for developing clinical practice guidelines, with reference to five authoritative guidelines used worldwide. PubMed, Cumulative Index to Nursing and Allied Health Literature, Ichushi-Web, and Cochrane Central Register of Controlled Trials were used for a systematic search of the literature. Eight clinical questions (CQs) were eventually established, and the strength of recommendation for each CQ is presented based on 867 references. The salient features of the Guideline are that it was jointly developed by three societies (Japanese Society of Cancer Nursing, Japanese Society of Medical Oncology, and Japanese Society of Pharmaceutical Oncology), contains descriptions including the definition of HDs and the concept of hierarchy of controls, and addresses exposure control measures during handling of chemotherapy drugs. Our future task is to collect additional evidence for the recommended exposure control measures and to assess whether publication of the Guideline has led to adherence of measures to prevent occupational exposure.

Effect of aromatase inhibitors on bone mineral density in a Japanese breast cancer population.

We retrospectively analyzed the bone mineral density (BMD) of postmenopausal Japanese women taking an aromatase inhibitor (AI), exemestane, anastrozole or letrozole, and calculated the decrease rate constant of BMD in each individual to compare the influence of the three AIs on BMD. We also aimed to evaluate the preventive effect of bisphosphonates (BPs) on the AI-induced decrease in BMD. The decrease rate constant of BMD (k(e)) in each individual was determined as a slope of linear regression of the relationship between time and logarithm of BMD value in each patient during the AI therapy. To compensate for the age-related change in BMD level, we estimated the age-related decrease rate constant of BMD (ke,0) in healthy Japanese postmenopausal women from the literature. AIs decreased BMD with a ke value of -0.0329 yr(-1), which was 4.7-fold larger than the k(e,0) value of -0.00699 yr(-1). No significant difference was detected in the influence on BMD among AIs. Co-administration of BP ameliorated the ke value to -0.0117 yr(-1), a value similar to k(e,0). The influence of AIs on BMD was quantitatively evaluated by using the decrease rate constant of BMD (k(e)). The present study also suggests that BPs may be useful to prevent the decrease in BMD induced by AIs.