Background:A British randomised study of gemcitabine plus cisplatin (GC) combination showed promising results in biliary tract cancer (BTC) patients. In our study, we evaluated the efficacy and safety of this combination compared with gemcitabine alone (G) in Japanese BTC patients.Methods:Overall, 84 advanced BTC patients were randomised to either cisplatin 25 mg m−2 plus gemcitabine 1000 mg m−2 on days 1, 8 of a 21-day cycle (GC-arm), or single-agent gemcitabine 1000 mg m−2 on days 1, 8 and 15 of a 28-day cycle (G-arm). Treatments were repeated for at least 12 weeks until disease progression or unacceptable toxicity occurred, up to a maximum of 48 weeks.Results:A total of 83 patients were included in the analysis. For the GC and G-arms, respectively, the 1-year survival rate was 39.0 vs 31.0%, median survival time 11.2 vs 7.7 months, median progression-free survival time 5.8 vs 3.7 months and overall response rate 19.5 vs 11.9%. The most common grade 3 or 4 toxicities (GC-arm/G-arm) were neutropenia (56.1%/38.1%), thrombocytopenia (39.0%/7.1%), leukopenia (29.3%/19.0%), haemoglobin decrease (36.6%/16.7%) and γ-GTP increase (29.3%/35.7%).Conclusions:Gemcitabine plus cisplatin combination therapy was found to be effective and well tolerated, suggesting that it could also be a standard regimen for Japanese patients.

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B‐cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti‐BAFF monoclonal antibody. This phase 1, multicenter, open‐label, nonrandomized, dose‐escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of tabalumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory MM (RRMM). Sixteen patients received intravenous i.v. tabalumab 100 mg (Cohort 1, n = 4) or i.v. tabalumab 300 mg (Cohort 2, n = 12) in combination with oral dexamethasone 20 mg/day and i.v. or s.c. bortezomib 1.3 mg/m2. All patients had treatment‐emergent adverse events (TEAE) possibly related to study treatment; the most common TEAE were thrombocytopenia (81.3%), lymphopenia (43.8%) and increased alanine aminotransferase (43.8%). Two (20.0%) dose‐limiting toxicities were observed, both in Cohort 2 (tabalumab 300 mg), which was below the predefined cutoff for tolerability (<33%). The pharmacokinetics of tabalumab were similar when bortezomib was coadministered i.v. versus s.c. The overall response rate was 56.3%, suggesting that the combined treatment was effective. In conclusion, combined treatment with these three agents was well tolerated in this population of Japanese patients with RRMM. The study was registered at www.clinicaltrials.gov (NCT01556438).

BackgroundMethotrexate (MTX) has been well-known anchor drug for rheumatoid arthritis (RA), however, dose regimen varies and it depends on countries. The divided dosage of MTX was frequently prescribed in Japan, however, the differences of safety and efficacy between divided and single dose regimens were not fully examined.ObjectivesWe conducted a preliminary study for RA patients to compare the safety, efficacy profile and MTX-polyglutamates (PGs) concentration between single- and divided dosage regimens.MethodsSingle-center Random Controlled Trial was designed. Thirty-one patients who had been insufficiently controlled by MTX (8 mg/week) were randomly assigned to 2 groups (single dose regimen/week: 15 patients; three-dose regimen/week: 16 patients). MTX dose of all patients was allowed to increase up to 16 mg/week. Safety and efficacy parameters (adverse events, the elevation of liver function tests (LFTs), WBC counts and DAS28 were monitored at baseline, 4, 8, 12 and 19 weeks. MTX-PGs in red blood cells were also detected by LC-MS/MS at same interval.ResultsThere were no significant differences in the average of age (66.3±9.2yr), disease duration (5.8yr), and baseline DAS28(CPR) (2.84±0.98) between two groups. There were also no differences in the improvement of DAS28(CPR) between two groups (-0.95±1.66 vs -0.75±1.09 respectively) and weekly MTX dose (11.5±1.6mg/week vs 11.4±1.4mg/week). Three adverse events were observed only in 3-dose regimen group (18.8%, increase in LTFs). The remarkable difference was observed in MTX-PGs, 3-dose regimen group showed significantly higher concentration of MTX-PG1+2 than single-dose group. On the other hand, 3-doses regimen group showed slight lower MTX-PG4+5 than single-dose regimen group, and there was no difference in MTX-PG3.ConclusionsThe efficacy did not show significant difference between two groups. Liver function may be affected by concentration of MTX-PG1+2, which elevated in divided dosage regimen group. Further investigation is required in a larger population.AcknowledgementsClinical registration: UMIN000012473Disclosure of InterestA. Ihata: None declared, K. Kobayashi: None declared, A. Osada: None declared, H. Sakuma: None declared, F. Tsuji Employee of: Santen Pharmaceutical. CO.,Ltd., T. Yoshimura Employee of: Santen Pharmaceutical. CO.,Ltd., C. Setoguchi Employee of: Santen Pharmaceutical. CO.,Ltd., M. Okamoto Employee of: Santen Pharmaceutical. CO.,Ltd., S. Nagaoka: None declared

Objective: To evaluate the long-term safety and effectiveness of biosimilar insulin glargine (GLY) in real-world clinical practice. Methods: This prospective, non-interventional, multicenter, observational, post-marketing safety study (PMSS) enrolled Japanese patients with type 1 or 2 diabetes mellitus (T1DM or T2DM) starting GLY therapy, and was required by Japanese Pharmaceutical Affairs Law mandating post-marketing safety surveillance to acquire safety and effectiveness data of biosimilar products. Data collected from the 12-month observation included patient characteristics, adverse events, and blood glucose control. Results: The study enrolled 141 patients with T1DM and 1104 patients with T2DM. Pre-study insulin was used by 94.1% of patients with T1DM and 75.0% with T2DM. 65.4% of patients with T1DM and 64.3% with T2DM switched from the reference product (GLY-switched), while 25.0% with T2DM were insulin-naive. Adverse events were reported by 5.7% and 8.5% in T1DM and T2DM, respectively. Similar incidences were reported in GLY-switched. Adverse events were reported by 10.7% in insulinnaive T2DM. Baseline mean hypoglycemic events/month were 1.8 and 0.1 in T1DM and T2DM, respectively: the mean change from baseline (CFB) was -1.2 (p ¼ .066) and 0.0 (p ¼ .915), respectively. Baseline mean HbA1c was 8.4% and 8.7% in T1DM and T2DM, respectively; the mean CFB was -0.5% (p < .001) and -0.9% (p < .001), respectively, and -1.5% (p < .001) in insulin-naive T2DM. Conclusions: This first long-term Japanese PMSS of GLY demonstrated adverse events, hypoglycemia, and glycemic control consistent with the known GLY profile for T1DM and T2DM patients, in routine clinical practice. ARTICLE HISTORY