First Report of a Patient With Natural Killer-Lymphoblastic Leukemia/Lymphoma in Korea

No abstract available.

Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. MATERIALS AND METHODS: Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue. RESULTS: In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07). CONCLUSION: OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Modifiers of TGF-beta1 effector function as novel therapeutic targets of pulmonary fibrosis

Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-beta1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-beta1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-beta1 could be an alternative approach that selectively inhibits TGF-beta1-stimulated fibrotic tissue response while preserving major physiological function of TGF-beta1. Recent studies from our laboratory revealed that TGF-beta1 crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-beta1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-beta1 plays a significant role.

A Phase II Study to Evaluate the Efficacy of Ramosetron, Aprepitant, and Dexamethasone in Preventing Cisplatin-Induced Nausea and Vomiting in Chemotherapy-Naive Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Combination therapy with aprepitant, serotonin receptor antagonist, and steroids improves the complete response rate of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, it is not known whether ramosetron is suitable for administration in combination with aprepitant. Therefore, we conducted a multicenter, open-label, prospective, phase II study in order to assess the efficacy and tolerability of combination therapy with ramosetron, aprepitant, and dexamethasone (RAD) for prevention of cisplatin-based CINV in chemotherapy-naive patients with solid cancers. MATERIALS AND METHODS: Forty-one patients with various solid cancers (31 male and 10 female; median age, 59 years) who received treatment with highly emetogenic chemotherapy (median cisplatin dose, 70 mg/m2; range 50 to 75 mg/m2) were enrolled in this study. Oral aprepitant (125 mg on day 1; 80 mg on days 2 and 3), intravenous ramosetron (0.6 mg on day 1), and oral dexamethasone (12 mg on day 1; 8 mg on days 2-4) were administered for prevention of CINV. RESULTS: The complete response (no emesisand retching and no rescue medication) rate was 94.9% in the acute period (24 hours post-chemotherapy), 92.3% in the delayed period (24-120 hours post-chemotherapy), and 92.3% in the overall period (0-120 hours). The absolute complete response (complete response plus no nausea) rate was 74.4% in the acute period, 51.3% in the delayed period, and 46.2% in the overall period. There were no grade 3 or 4 toxicities related to these antiemetic combinations. CONCLUSION: RAD regimen is a safe and effective antiemetic treatment for prevention of CINV in patients receiving highly emetogenic chemotherapy.

The Efficacy of Inhaled Corticosteroid on Chronic Idiopathic Cough / 결핵및호흡기질환

BACKGROUND: The discomfort caused by chronic cough, that is persistent for more than 3 weeks, causes a number of patients to seek medical attention. However, the underlying disorder often remains undetermined despite thorough examinations, and is considered to be idiopathic. This study compared the efficacy of inhaled corticosteroid with conventional cough suppressants on chronic idiopathic cough. METHODS: Eligible patients with chronic idiopathic cough were randomly assigned to either the inhaled fluticasone group or the codeine plus levodropropizine oral administration group. The subjects in each group took their planned medication for 2 weeks. After the trial, comparative analyses of outcomes were performed in terms of the remnant cough (%) at the end of treatment, drug compliance, and adverse drug events. RESULTS: Seventy-seven patients were enrolled in this randomized trial; 38 to the inhaled fluticasone group and 39 to the codeine plus levodropropizine group. The remnant cough was 41.0+/-35.8% in the inhaled fluticasone group, and 32.4+/-32.0% in the codeine+levodropropizine group (p=0.288). Drug compliance was 95.4+/-7.4% and 81.8+/-18.6% in the inhaled fluticasone and the codeine+levodropropizine group, respectively (p<0.001). Nine patients had adverse drug events in the codeine+levodropropizine group compared to one in the inhaled fluticasone group (p<0.001). CONCLUSION: Short-term inhaled corticosteroid is not inferior to conventional antitussive agents in controlling chronic idiopathic cough without significant adverse events.

The Efficacy of Inhaled Corticosteroid on Chronic Idiopathic Cough / 결핵및호흡기질환

BACKGROUND: The discomfort caused by chronic cough, that is persistent for more than 3 weeks, causes a number of patients to seek medical attention. However, the underlying disorder often remains undetermined despite thorough examinations, and is considered to be idiopathic. This study compared the efficacy of inhaled corticosteroid with conventional cough suppressants on chronic idiopathic cough. METHODS: Eligible patients with chronic idiopathic cough were randomly assigned to either the inhaled fluticasone group or the codeine plus levodropropizine oral administration group. The subjects in each group took their planned medication for 2 weeks. After the trial, comparative analyses of outcomes were performed in terms of the remnant cough (%) at the end of treatment, drug compliance, and adverse drug events. RESULTS: Seventy-seven patients were enrolled in this randomized trial; 38 to the inhaled fluticasone group and 39 to the codeine plus levodropropizine group. The remnant cough was 41.0+/-35.8% in the inhaled fluticasone group, and 32.4+/-32.0% in the codeine+levodropropizine group (p=0.288). Drug compliance was 95.4+/-7.4% and 81.8+/-18.6% in the inhaled fluticasone and the codeine+levodropropizine group, respectively (p<0.001). Nine patients had adverse drug events in the codeine+levodropropizine group compared to one in the inhaled fluticasone group (p<0.001). CONCLUSION: Short-term inhaled corticosteroid is not inferior to conventional antitussive agents in controlling chronic idiopathic cough without significant adverse events.

Role of Methacholine PC20 in FEF(25-75%) for the Diagnosis of Bronchial Asthma / 결핵및호흡기질환

BACKGROUND: The methacholine bronchial provocation test is a useful tool for evaluating asthma in patients with normal or near normal baseline lung function. However, the sensitivity of this test is 82~92% at most. The purpose of this study is to evaluate the clinical usefulness of FEF(25-75%) in identification of airway hyperresponsiveness in patients with suspected asthmatic symptoms. METHODS: One hundred twenty-five patients who experienced cough and wheezing within one week prior to their visiting the clinic were enrolled. RESULTS: Sixty-four subjects showed no significant reduction of FEV1 or FEF(25-75%) on the methacholine bronchial provocation test (Group I). In 24 patients, FEF(25-75%) fell more than 20% from baseline without a 20% fall of FEV1 during methacholine challenge (Group II). All patients who had more than 20% fall of FEV1 (n=37) also showed more than 20% of reduction in FEF(25-75%) (Group III). Baseline FEV1/FVC (%) and FEF(25-75%) (L) were higher in group II than group III (81.51+/-1.56% vs. 75.02+/-1.60%, p<0.001, 3.25+/-0.21 L vs. 2.45+/-0.21 L, p=0.013, respectively). Group II had greater reductions of both FEV1 and FEF(25-75%) than group I at 25 mg/mL of methacholine (p<0.001). The provocative concentration of methacholine causing a 20% fall in FEF(25-75%) in group II was about three-fold higher than that in group III. CONCLUSION: A 20% fall of FEF(25-75%) by methacholine provocation can be more sensitive indicator for detecting a milder form of airway hyperresponsiveness than FEV1 criteria.