Showing papers by "Yoshikazu Inoue published in 2013"

Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan.

Abstract: Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated. All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used. In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma. Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

Cytomegalovirus infection during immunosuppressive therapy for diffuse parenchymal lung disease.

Abstract: Background and objective: Cytomegalovirus (CMV) infection is a life-threatening condition in patients with diffuse parenchymal lung diseases (DPLDs), who are receiving immunosuppressive therapy. The aim of this study was to describe the clinical features of CMV infection and to propose a strategy for managing CMV infection in patients with DPLD who are receiving immunosuppressive therapy. Methods: A retrospective longitudinal observational study was performed on 69 patients with DPLDs (39 with acute/subacute onset, 30 with chronic onset) who were receiving immunosuppressive therapy and were positive for CMV pp65 antigen (CMV-pp65Ag) in peripheral blood leukocytes (PBLs). Results: Clinical CMV disease and subclinical CMV antigenaemia developed in 23 and 46 patients, respectively. The cut-off level of CMV-pp65Ag indicating clinical CMV disease, as determined by receiver operator characteristic curve analysis, was 7.5 cells per 5 × 104 PBLs. Multivariate analysis revealed that early CMV infection was associated with acute/subacute onset of underlying DPLD and with respiratory dysfunction at the commencement of immunosuppressive therapy. Multivariate analysis also suggested that the acute/subacute onset of underlying DPLD, a CMV-pp65Ag titre of >7.5 cells per 5 × 104 PBLs, and C-reactive protein levels ≥10 mg/L indicated a poor prognosis. Conclusions: We recommend that CMV-pp65Ag antigenaemia of >7.5 cells per 5 × 104 PBLs in patients with DPLD should be treated with ganciclovir. Patients with lower levels of CMV-pp65Ag antigenaemia should be closely monitored or treated with ganciclovir if the clinical findings suggest a poor prognosis.

All-case post-marketing surveillance (PMS) of pirfenidone in Japan: Clinical characteristics, efficacy and safety profile in >1300 patients with idiopathic pulmonary fibrosis (IPF)

Abstract: Background: In 2008, a novel anti-fibrotic agent, pirfenidone (PFD, Pirespa®) was approved for the treatment of IPF in Japan. Aims and objectives: After the approval in 2008, the PMS was conducted under government requirement to access the clinical characteristics, efficacy and safety profile of PFD in Japanese clinical setting. Methods: All patients (pts) who initiated PFD therapy from Dec 2008 to Oct 2009 in Japan were enrolled. All adverse drug reactions (ADR) were collected. The efficacy was evaluated on the changes in vital capacity (VC) from baseline. All cases who were enrolled were analyzed up to 1 year from the first dose. Results: The data on 1256 cases were locked by Oct 2012; 1247 cases were evaluable for safety. Mean age of pts was 69.4 yrs; 28.1% were 75 yr or older. At baseline (using Japanese severity grade of IPF), 40.7% of pts were diagnosed as grade IV {(PaO2 at rest <60 Torr) or (PaO2 at rest <70 Torr and 6MWT SpO2 <90%)}. 60.6% of pts continued PFD therapy for 6 months or longer. Incidences of decreased appetite, photosensitivity reaction and nausea were 29.0%, 15.0% and 8.3%, respectively. Among pts treated with PFD for 6 months or longer, the mean change in VC was -0.07 L (median interval of measure: 278 days). The data will be updated at the congress. Conclusions: Our data from the largest PMS of PFD to date showed that PFD was tolerable and kept the decline in VC to a minimum. Although most ADRs were manageable, the control of gastrointestinal symptoms was thought to be of importance in order that therapy could be continued and maximal benefit from PFD could be gained.

A comorbid case of multicentric Castleman's disease and pulmonary hyalinising granuloma successfully treated with tocilizumab and corticosteroid

Abstract: A 49-year-old man with superficial lymphadenopathy presented with symptoms of low-grade fever, general fatigue and weight loss. On examination, multiple superficial lymphadenopathies and brown macules were observed on the trunk. Laboratory studies revealed an elevation of serum C reactive protein and interleukin 6 (IL-6) in addition to polyclonal hyperimmunoglobulinaemia. High-resolution CT of the chest showed bilateral multiple nodules and patchy ground-glass opacities with interstitial thickening. Biopsy of the cervical lymph node and skin biopsy showed numerous perivascular plasma cells, which were characteristic of the plasma cell type of Castleman's disease. Surgical lung biopsy showed hyalinising granuloma, which are hyalinous nodular lesions surrounded by lymphoid cells. He was diagnosed with multicentric Castleman's disease complicated by pulmonary hyalinising granulomas; his symptoms improved by treatment with tocilizumab, which is a humanised antihuman IL-6 receptor monoclonal antibody and corticosteroid. This is the first report of a comorbid case successfully treated with tocilizumab and corticosteroid.