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Amagasaki, Japan

Hayashi N.,Kansai Rosai Hospital | Okanoue T.,Saiseikai Suita Hospital | Tsubouchi H.,Kagoshima University | Toyota J.,Sapporo Kosei General Hospital | And 2 more authors.
Journal of Viral Hepatitis | Year: 2012

The aims of this phase III study were to assess the efficacy and safety of telaprevir in combination with peginterferon alfa-2b (PEG-IFN) and ribavirin (RBV) for difficult-to-treat patients who had not achieved sustained virological response (SVR) to prior regimens in Japan. The subjects were 109 relapsers (median age of 57.0 years) and 32 nonresponders (median age of 57.5 years) with hepatitis C virus genotype 1. Patients received telaprevir (750 mg every 8 h) for 12 weeks and PEG-IFN/RBV for 24 weeks. The SVR rates for relapsers and nonresponders were 88.1% (96/109) and 34.4% (11/32), respectively. Specified dose modifications of RBV that differed from that for the standard of care were introduced to alleviate anaemia. RBV dose reductions were used for 139 of the 141 patients. The SVR rates for relapsers did not depend on RBV dose reduction for 20-100% of the planned dose (SVR rates 87.5-100%, P < 0.05). Skin disorders were observed in 82.3% (116/141). Most of the skin disorders were controllable by anti-histamine and/or steroid ointments. The ratios of discontinuation of telaprevir only or of all the study drugs because of adverse events were 21.3% (30/141) and 16.3% (23/141), respectively. A frequent adverse event leading to discontinuation was anaemia. Telaprevir in combination with PEG-IFN/RBV led to a high SVR rate for relapsers and may offer a potential new therapy for nonresponders even with a shorter treatment period. © 2011 Blackwell Publishing Ltd. Source

Kumada H.,Toranomon Hospital | Toyota J.,Sapporo Kosei General Hospital | Okanoue T.,Saiseikai Suita Hospital | Chayama K.,Hiroshima University | And 2 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: To evaluate the efficacy and safety of telaprevir in combination with peginterferon-α2b (PEG-IFN) and ribavirin (RBV) in patients with chronic hepatitis C. Methods: In a multi-center randomized clinical trial in Japan, on patients infected with HCV of genotype 1, 126 patients were assigned to telaprevir for 12 weeks along with PEG-IFN and RBV for 24 weeks (Group A), while 63 to PEG-IFN and RBV for 48 weeks (Group B). Results: HCV RNA disappeared more swiftly in patients in Group A than B, and the frequency of patients without detectable HCV RNA at week 4 (rapid virological response (RVR)) was higher in Group A than B (84.0% vs. 4.8%, p <0.0001). Grade 3 and 4 skin disorders, including Stevens-Johnson syndrome and drug rashes with eosinophilia and systemic symptoms, as well as Grade 3 anemia (<8.0 g/dl), occurred more frequently in Group A than B (skin disorders, 11.9% vs. 4.8%; anemia, 11.1% vs. 0.0%). The total RBV dose was smaller in Group A than B (47.0% vs. 77.7% of the target, p <0.0001). Despite these drawbacks, sustained virological response (SVR) was achieved more frequently in Group A than B (73.0% vs. 49.2%, p = 0.0020). Conclusions: Although the triple therapy with telaprevir-based regimen for 24 weeks resulted in more adverse events and less total RBV dose than PEG-IFN and RBV for 48 weeks, it was able to achieve higher SVR within shorter duration by carefully monitoring adverse events and modifying the RBV dose as required. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan. Erlotinib plus gemcitabine( GEM) combination therapy provided significant improvements in the overall and progression-free survival in a phase III trial in Canada and a phase II trial in Japan. As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of erlotinib plus GEM in patients with unresectable pancreatic cancer. GEM at a dose of 1,000 mg/m2 was administered on days 1, 8, and 15 in a 4-week cycle. Erlotinib was taken orally at 100 mg/day until disease progression or unmanageable toxicity. Between October 2011 and April 2013, 9 patients were enrolled. The mean age was 62.3 years (range, 48-70 years), and 66.7% of patients were men. Eight patients had no prior therapy. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0. Eight patients had metastatic and 1 had locally advanced disease. Five patients had a history of smoking. The median duration of erlotinib administration was 133 days, and the median dose intensity was 100 mg/day, with the majority of patients( 88.9%) receiving 100% of the relative dose intensity. The median duration of GEM treatment was 5 cycles, and its median dose intensity was 890 mg/m2/week, with approximately half of the patients (66.7%) receiving >85% of the relative dose intensity. The most frequently reported adverse event was skin rash, which occurred in 44.4% of the patients. Other common non-hematological adverse events included facial edema, diarrhea, nausea, depilation, pruritus, and cholangitis. Most patients experienced some degree of hematological toxicity, with Grade 3 or 4 neutropenia, leukopenia, and anemia. Interstitial lung disease was not observed. The median overall survival was 7.63 months, and the 1-year survival rate was 15%. The median progression-free survival was 5.60 months. The overall response rate was 11.1%,and the disease control rate was 88.9% [complete response (CR), n =0; partial response( PR), n=1; stable disease( SD), n=7]. In conclusion, erlotinib plus GEM combination therapy is well tolerated and associated with efficacy and survival outcomes. Source

Takamura E.,Tokyo Womens Medical University | Tsubota K.,Keio University | Watanabe H.,Kansai Rosai Hospital | Ohashi Y.,Ehime University
British Journal of Ophthalmology | Year: 2012

Aims: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in dry eye patients, using mean changes in fluorescein and rose bengal staining scores as endpoints. Trial design and methods: In this multicenter, randomised, double-masked, parallel study of 286 dry eye patients with fluorescein and rose bengal staining scores of ≥3 were randomised to the treatment groups in a 1:1 ratio. Efficacy and safety were evaluated after drop-wise instillation of the study drug, six times daily for 4 weeks. Results: After 4 weeks, the intergroup difference in the mean change from baseline in fluorescein staining score was -0.03; this verified the non-inferiority of diquafosol. The mean change from baseline in rose bengal staining score was significantly lower in the diquafosol group (p=0.010), thus verifying its superiority. The incidence of adverse events was 26.4% and 18.9% in the diquafosol and sodium hyaluronate groups, respectively, with no significant difference. Conclusions: Diquafosol (3%) and sodium hyaluronate (0.1%) exhibit similar efficacy in improving fluorescein staining scores of dry eye patients, whereas, diquafosol exhibits superior efficacy in improving rose bengal staining scores. Diquafosol has high clinical efficacy and is well tolerated with a good safety profile. Source

Low-grade cribriform cystadenocarcinoma (LGCCA) is a rare tumor of the salivary gland that exhibits clinically indolent behavior. In this paper, we present a case of invasive adenocarcinoma of the accessory parotid gland in a young male that exhibited histology suggestive of an association of LGCCA. A 27-year-old man presented with a subcutaneous tumor in his left cheek. The tumor was separated from the parotid gland and located on the masseter muscle. The tumor was resected, and the postoperative histological diagnosis was adenocarcinoma, not otherwise specified (ANOS). The tumor exhibited papillary-cystic and cribriform proliferation of the duct epithelium and obvious stromal infiltration. Some tumor nests were rimmed by myoepithelium positive for smooth muscle actin, p63, and cytokeratin 14, indicating the presence of intraductal components of the tumor. Tumor cells exhibited mild nuclear atypia, and some of them presented an apocrine-like appearance and had cytoplasmic PAS-positive/diastase-resistant granules and hemosiderin. Other cells had foamy cytoplasm with microvacuoles. Immunohistochemistry revealed that the almost all of the tumor cells were strongly positive for S-100. These histological findings suggest the possibility that ANOS might arise secondarily from LGCCA. This is an interesting case regarding the association between ANOS and LGCCA in oncogenesis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1226764594634693. Source

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