Full-dose sofosbuvir plus low-dose ribavirin for hepatitis C virus genotype 2-infected patients on hemodialysis.

BACKGROUND/AIMS: New direct-acting antivirals have shown surprising success in the treatment of hepatitis C, not only in the general population, but also in difficult-to-treat cohorts. However, there is still limited data regarding direct-acting antivirals, including sofosbuvir (SOF), in the context of hemodialysis. The aim of this study was to investigate the safety and outcome of administering full-dose SOF (400 mg/day) plus low-dose ribavirin (RBV, 100 to 200 mg/day) in hemodialysis patients with hepatitis C virus (HCV) genotype 2 (GT2) infection. METHODS: Patients with chronic HCV GT2 infection and end-stage renal disease on maintenance hemodialysis treated with full-dose SOF plus low-dose RBV were retrospectively identified from a database of patients with HCV GT2 who were treated in Konkuk University Chungju Hospital between February 2017 and February 2018. Medical records were reviewed for demographics, medical history, laboratory data, and radiologic and electrocardiographic findings. RESULTS: All nine patients completed a full course of 12 weeks of treatment with a full-dose SOF plus low-dose RBV regimen. Two had compensated cirrhosis. Seven patients were treatment-naïve, and two had a relapse following previous interferon-based therapy. All patients had a sustained viral response at 12 weeks post-treatment. There was no discontinuation of treatment because of side effects. CONCLUSION: In hemodialysis patients with HCV GT2 infection, the full-dose SOF plus low-dose RBV regimen appears to be safe and well tolerated, and yields high rates of sustained virologic response.

Tyrosine Kinase Inhibitor Dosing Patterns in Elderly Patients With Chronic Myeloid Leukemia.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) improve the survival rate of patients with chronic myeloid leukemia (CML). However, elderly patients often experience adverse events and require dose adjustments, leading to dose interruptions or treatment discontinuation. We therefore investigated TKI dosing patterns and subsequent outcomes in elderly CML patients. PATIENTS AND METHODS: Using the National Health Information Database, we identified patients with CML aged ≥ 70 years who were prescribed TKIs (imatinib, dasatinib, nilotinib, or radotinib) during 2007-2013. Data on age, sex, prescribed medication, and date of death were extracted. RESULTS: Among the 378 patients, the median age was 75 (range, 70-92) years; the median follow-up period was 53 (range, 1-133) months. Imatinib, dasatinib, nilotinib, and radotinib were prescribed to 324 (85.7%), 110 (29.1%), 93 (24.6%), and 15 (4.0%) patients, respectively. In 42 patients (12.2%), the initial dose was lower than the recommended dose for chronic-phase CML. At last follow-up, 249 patients (65.9%) were receiving a reduced dose. The mean ± standard deviation dose densities of imatinib, dasatinib, nilotinib, and radotinib were 207 ± 121.6, 29 ± 26.7, 235 ± 197, and 123 ± 95.4 mg/day, respectively. The estimated 5-year overall survival probability was 61.0%. Initial TKI dose or dose reduction within first year did not affect the overall survival (P = .0571 and .1826, respectively). CONCLUSION: Dose reduction was observed in 65.9% of the patients at their last visit; except for imatinib, TKI dose densities were < 50% of the recommended dose for the chronic phase. Therefore, the recommended TKI doses might be too high for elderly patients with CML.

Early venous thromboembolism at the beginning of palliative chemotherapy is a poor prognostic factor in patients with metastatic pancreatic cancer: a retrospective study.

BACKGROUND: This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. METHODS: A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. RESULTS: VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (< 135 mmol/L) and high Khorana score (≥3) were strong predictive factors of early VTE (odds ratio [OR] 5.109; 95% confidence interval [95% CI] = 1.010-25.845; p = 0.049 for Khorana score, OR 10.304; 95% CI = 1.036-102.466; p = 0.047) for hyponatremia). CONCLUSIONS: Our study demonstrated that occurrence and detection of VTE in the early period of chemotherapy was the most significant VTE-related prognostic factor in patients with metastatic pancreatic cancer receiving chemotherapy. Prediction using the Khorana score and serum Na levels would be helpful in early diagnosis of VTE.

Clinical impact of the early alanine amininotransferase flare during tenofovir monotherapy in treatment-naïve patients with chronic hepatitis B.

BACKGROUND/AIMS: Little is known about the effect of early flares on response during first-line tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB). The aim of this study was to investigate the incidence and outcome of early alanine aminotransferase (ALT) flare in treatment-naive patients with CHB during long-term TDF monotherapy. METHODS: One hundred eighty-one treatment-naive CHB patients were treated with a 300-mg once-daily dose of TDF for more than 12 weeks. Virological markers of hepatitis B virus (HBV) and biochemical data were measured at baseline and every 4-12 weeks during the therapy. The proportion of patients with undetectable HBV DNA level (< 100 copies/mL) was noted. RESULTS: The median age was 48.3 years and 122 patients (67.4%) were men. Hepatitis B envelope antigen (HBeAg) was positive in 101 patients (55.8%). No patient had cirrhosis. The median follow-up duration was 45 weeks (12-155 weeks). ALT flare (>5 × upper limit of the normal range) occurred in seven patients (3%) without viral breakthrough within the first 8 weeks after the start of TDF monotherapy. Among them, six patients were HBeAg-positive and one patient was HBeAg-negative. All cases of early ALT flares resolved within 4 weeks and virologic response was observed in all patients without interruption or discontinuation of treatment. CONCLUSIONS: Continuous TDF monotherapy was effective and safe in treatment-naive patients with CHB who experienced early ALT flares followed by a decrease in HBV DNA level.

Reversible splenial lesion on the corpus callosum in nonfulminant hepatitis A presenting as encephalopathy.

Reversible focal lesions on the splenium of the corpus callosum (SCC) have been reported in patients with mild encephalitis/encephalopathy caused by various infectious agents, such as influenza, mumps, adenovirus, Varicella zoster, Escherichia coli, Legionella pneumophila, and Staphylococcus aureus. We report a case of a reversible SCC lesion causing reversible encephalopathy in nonfulminant hepatitis A. A 30-year-old healthy male with dysarthria and fever was admitted to our hospital. After admission his mental status became confused, and so we performed electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain, which revealed an intensified signal on diffusion-weighted imaging (DWI) at the SCC. His mental status improved 5 days after admission, and the SCC lesion had completely disappeared 15 days after admission.

Leukemia cutis in a patient with acute monocytic leukemia diagnosed simultaneously with hepatocellular carcinoma: A case study.

Acute myeloid leukemia presenting as leukemia cutis (LC) with hepatocellular carcinoma is extremely rare. The current study presents a case of a 53-year-old male with generalized cutaneous nodules on the face and anterior chest wall. Laboratory tests, including bone marrow biopsy revealed acute myelomonocytic leukemia (AML-M4) with skin and tonsilar involvement. Liver magnetic resonance imaging (MRI) revealed a 6-cm mass in hepatic segments 4 and 8, and a liver biopsy demonstrated that hepatocellular carcinoma cells and immature blast cells coexisted. Although LC has been reported in Korea, a case of LC associated with acute myelomonocytic leukemia was diagnosed simultaneously with hepatocellular carcinoma and tonsillar involvement. The present study describes this case with a review of the literature.

Phase II study of vinorelbine monotherapy in anthracycline and taxane pre-treated metastatic breast cancer.

We performed a single-institution phase II study to evaluate the efficacy and toxicities of vinorelbine monotherapy in patients previously treated with anthracyclines and taxanes. Vinorelbine was administered at a dose level of 25 mg/m² intravenously on days 1, 8, 15 and 22, every four weeks, and responses were assessed after every two cycles of treatment. All of the patients had previously been treated with anthracyclines and taxanes. A total of 26 patients were enrolled in this study between April 2004 and August 2009. The median age of the patients was 47 years (range, 37 to 71 years), and 80.8% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Out of 24 evaluable patients, five partial responses were observed, giving an overall response rate of 20.8%, with a median response duration of 2.8 months. The median time to progression was 3.7 months (range, 0.5 to 22.6 months), and median overall survival duration was 10.4 months (range, 1.3 to 57.6 months). The major toxicities observed were neutropenia, anemia and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in 18 patients (69.2%) and anemia in four patients (15.3%). Grade 1 or 2 peripheral neuropathy was observed in 11 patients (42.3%), however there were no cases of grade 3 or 4 peripheral neuropathy. The results of this study indicate that vinorelbine monotherapy was feasible regimen with manageable toxicities in patients with metastatic breast cancer who were previously exposed to anthracyclines and taxanes.

Prognostic significance of serum vascular endothelial growth factor per platelet count in unresectable advanced gastric cancer patients.

OBJECTIVE: Angiogenesis is one of the crucial steps in various solid tumor growth and metastasis. However, there are limited data regarding the clinical and prognostic significance of serum vascular endothelial growth factor levels per platelet count in unresectable advanced gastric cancer compared with early gastric cancer and healthy volunteers. METHODS: A total of 181 gastric cancer patients were included and control serum samples were acquired from 113 healthy volunteers. The levels of serum vascular endothelial growth factor were measured using human vascular endothelial growth factor quantitative enzyme-linked immunosorbent assay. Survival curves were calculated using the Kaplan-Meier method and survival comparisons were made by the log-rank test in metastatic gastric cancer. RESULTS: There was a significant correlation between serum vascular endothelial growth factor levels and differentiation of tumor (P = 0.014), stage (P = 0.036). The overall survival (P = 0.0432) and the progression-free survival (P = 0.0116) were significantly shorter in patients with high serum vascular endothelial growth factor per platelet count (≥1.626 pg/10(6)). In the multivariate analysis, the presence of peritoneal carcinomatosis (P = 0.039), serum vascular endothelial growth factor per platelet (P = 0.005) were found to be significantly associated with poor progression-free survival. CONCLUSIONS: This study demonstrates that serum vascular endothelial growth factor per platelet count is correlated with poor overall survival and progression-free survival in patients with advanced gastric cancer.

Concurrent chemoradiation followed by adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma in Korea.

PURPOSE: Concomitant approach using cisplatin and 5-fluorouracil (5-FU) has shown an excellent local control rate and significantly reduced distant metastasis in patients with locally advanced nasopharyngeal carcinoma (NPC). However, optimal schedule and dosing of chemotherapy still need to be developed to reduce distant metastasis. This retrospective study was conducted to evaluate the efficacy, toxicity, and tolerability of a concurrent chemoradiation therapy (CCRT) regimen using cisplatin and 5-FU followed by adjuvant chemotherapy (AC) in patients with locoregionally advanced NPC. METHODS: Forty-three NPC patients who had AJCC stage T3/T4 or N2/N3 and M0 disease were evaluated. The chemotherapy during CCRT consisted of cisplatin (75 mg/m(2) on day 1) plus 5-FU (750 mg/m(2)/day on day 1-5), delivered every 4 weeks for two cycles. Three cycles of AC were given with cisplatin (75 mg/m(2)), epirubicin (37.5 mg/m(2)) on day 1, and bleomycin (7.5 mg/m(2) bolus iv. on day 1 followed by 9 mg/m(2) on day 1-5 by continuous infusion) every 3 weeks. RESULTS: The overall response rate after CCRT was 95% (22 CRs and 19 PRs in 43) and 100% (16 CRs and 8 PRs in 24) after AC. Grade 3/4 neutropenia, mucositis, and weight loss were observed during CCRT phase in 18, 44, and 26% of patients, respectively. AC caused grade 3/4 neutropenia and emesis in 12.5 and 20.8% of patients, respectively. CONCLUSIONS: CCRT regimen using cisplatin and 5-FU followed by three cycles of BEC chemotherapy was effective in locally advanced NPC patients, with acceptable and reversible acute toxicities.

Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression.

Bone morphogenetic protein-2 (BMP-2) was reported to enhance migration, invasion, and metastasis at the various types of cancer cells. The purpose of this study is to identify the role of BMP-2 in progression of gastric cancer. Forty-four patients with operable gastric cancer were enrolled. Also, twenty healthy volunteers were enrolled as control group. All patients received gastrectomy with D2 lymphadenectomy, and surgical staging was performed. Whole blood was obtained preoperatively in all patients, and serum BMP-2 levels were quantified by commercially available ELISA kit. Immunohistochemical stain for BMP-2 in all gastric cancer tissues was performed using tissue microarray. All patients showed increased serum BMP-2 levels compared with control group, when upper normal limit was defined as the mean of control serum level+2×standard deviation. The mean serum BMP-2 level of lymph node positive group was significantly elevated than that of lymph node-negative group (382.7 pg/ml, 95% CI 341.99-423.4 pg/ml vs 211.69 pg/ml, 95% CI 191.09-232.29 pg/ml, P<0.001). The serum BMP-2 was strongly correlated with the depth of invasion (T stage) and the extent of regional lymph node involvement (N stage) (r=0.662, P<0.001 and r=0.831, P<0.001, respectively). Moreover, the serum BMP-2 was correlated with the grade of tumor histology(r=0.421, P=0.008). Immunohistochemical stain showed the specific expression of BMP-2 in cancer cells compared with normal gastric mucosa. In conclusion, serum BMP-2 is associated with progression from early localized gastric cancer to locally advanced gastric cancer.

Complete remission in a patient with human herpes virus-8 negative multicentric Castleman disease using CHOP chemotherapy.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder. Although MCD pathogenesis is unclear, studies have suggested that human herpesvirus 8 (HHV-8) may be associated with the disorder. Recent reports have identified MCD cases without viral infection. A 43-year-old woman presented to our hospital for fever and myalgia of 6 months' duration. The complete blood count revealed an elevated leukocyte count (15.1x10(3)/microL) and a decreased hemoglobin level of 10.0 g/dL. The C-reactive protein level was elevated at 276.5 mg/L. Thoracic computed tomography (CT) scans revealed bilateral axillary lymphadenopathy. There was no evidence of HHV-8, human immunodeficiency virus (HIV), or Mycobacterium infection. Histologic evaluation of a lymph node biopsy from the left axilla yielded a diagnosis of MCD. Cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) were administered for a total of 4 cycles. The patient's fever and lymphadenopathy resolved after the course of chemotherapy. She has been in complete remission for 24 months at this writing. As previously reported, this case report suggests that MCD can develop without viral infection. CHOP chemotherapy may be an effective treatment option for newly diagnosed MCD patients.

Phase I dose escalation study of docetaxel with a fixed dose of S-1 in combination chemotherapy for advanced gastric cancer.

BACKGROUND: The primary objectives of this study were to estimate the maximum-tolerated dose (MTD) of docetaxel in combination with a fixed dose of S-1 and to determine the recommended dose (RD). PATIENTS AND METHODS: Patients with histologically proven gastric carcinoma with metastatic or locally advanced inoperable disease were eligible. Patients received intravenous docetaxel starting at 40 mg/m(2) (dose level 1), and stepwise dose increases to 50, 60, and 70 mg/m(2) were planned for successive patient cohorts (dose levels 2, 3, and 4, respectively) over 1 h on day 1 and oral S-1 administered at a fixed dose of 40 mg/m(2) twice daily on days 1-14, both drugs every 21 days. RESULTS: A total of 13 patients were enrolled into this trial. All three patients at dose level 3 developed dose-limiting toxicities (DLT), and this level was declared to be the MTD. Hence, level 2 (docetaxel 50 mg/m(2)) was declared to be the RD for the next study. As 9 of the 13 enrolled patients responded to treatment, the overall objective response rate was 69.2% (95% CI, 44.1-94.3%). The median time to progression was 8.38 months (range 1.44-8.51) and the overall survival duration was 9.9 months (range 0.62-11.57). The most common grade 3/4 toxicity of docetaxel plus S-1 was neutropenia, which was tolerable and manageable. CONCLUSION: This regimen showed encouraging activity and a manageable safety profile in advanced gastric carcinoma and could be used in further randomized studies.

Treatment outcomes of oxaliplatin, 5-FU, and leucovorin as salvage therapy for patients with advanced or metastatic gastric cancer: a retrospective analysis.

PURPOSE: We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer. METHODS: Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m(2) and LV 100 mg/m(2) (2-h intravenous infusion) followed by 5-FU 2,400 mg/m(2) (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles. RESULTS: Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32-76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths. CONCLUSION: The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients.