Seong Hoon Shin

Clinical Correlation between Brain Natriutetic Peptide and Anthracyclin-induced Cardiac Toxicity

PURPOSEnAnthracycline can effectively treat hematologic malignancies, but has significant risk of cardiotoxicity. We measured the clinical correlation between brain natriuretic peptide (BNP) and anthracycline-induced cardiotoxicity.nnnMATERIALS AND METHODSnBetween March 2005 and March 2007, 86 patients with acute leukemia, malignant lymphoma, or multiple myeloma receiving systemic chemotherapy with anthracycline were enrolled in the Department of Hemato-oncology, Kosin University Gospel Hospital. We investigated the relationship between BNP level and cardiotoxicity through echocardiography, electrocardiography, BNP levels, and symptoms of heart failure at each chemotherapy cycle.nnnRESULTSnOf the 86 participants (mean age, 48.5 years; range 20 approximately 65 years), cardiotoxicity developed in 21 patients (24.4%), with 2 patients showing arrhythmia only, 17 patients with transient aspects of heart failure, and 2 patients with chronic heart failure. Cardiotoxicity related to serum BNP level, age, cumulative dose of anthracycline, accompanying chronic disease, and elevated level of troponin-I. Heart failure was more common if BNP levels reached 100 pg/ml at least once.nnnCONCLUSIONSnThe clinical correlation between BNP and cardiotoxicity was significant in patients with systemic anthracycline chemotherapy. A prospective clinical trial will be needed to identify the causal relationship between serum BNP level and cardiotoxicity.

Intestinal Perforation in Colorectal Cancers Treated with Bevacizumab (Avastin

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), and it has shown promise as a clinical agent against metastatic colorectal cancer, and particularly in combination with chemotherapy. Bowel perforation is a known risk thats associated with bevacizumab use, but the etiology is unknown. Here we report on two cases of metastatic colorectal cancer in which the patients suffered from intestinal perforation after chemotherapy with bevacizumab. For the first case, a 47 year-old man had rectal cancer with concurrent liver and lung metastasis. He underwent chemotherapy with 5-fluorouracil, irinotecan and bevacizumab. Fever and abdominal pain developed seven days later, and rectal perforation was identified upon exploration 13 days later. For the second case, a 48 year-old woman had sigmoid colon cancer with peritoneal and ovary metastases. After seven days of chemotherapy with 5-fluorouracil, oxaliplatin and bevacizumab, exploratory surgery revealed a perforation at the ileum.

A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma

BackgroundThe aim of this study was to examine the efficacy and safety of everolimus in patients with progressive unresectable adenoid cystic carcinoma (ACC).MethodsHistologically confirmed ACC patients with documented disease progression within 12xa0months prior to the study entry were eligible. Everolimus was given at a dose of 10xa0mg daily until progression or occurrence of unacceptable toxicities. The primary endpoint was a 4-month progression-free survival (PFS).ResultsA total of 34 patients were enrolled. The 4-month PFS probability was 65.5% (95% one-sided confidence interval [CI], 47.7 to infinity). Median PFS duration was 11.2xa0months (95% CI, 3.6 to 15.8). Complete or partial response was not achieved. Twenty-seven (79.4%, 95% CI, 63.2 to 89.6) patients showed stable disease (SD). Tumor shrinkage within SD criteria was observed in 15 patients (44.1%) and SD lasting 6xa0months was observed in 13 patients (38.2%). Four patients had disease progression. Among the 18 patients with both pre- and post-treatment (at 8xa0weeks) FDG-PET scans available, 8 patients (44.4%) showed a partial metabolic response, defined as a ≥25% reduction in maximum standardized uptake values (SUVmax). The most common adverse events were stomatitis, anemia, asthenia, and leukopenia. No unexpected everolimus related toxicities were reported.ConclusionsEverolimus showed promising efficacy and good tolerability in progressive unresectable ACC.Trial registrationClinicalTrials.gov identifier, NCT01152840

An open label, multicenter, phase II study of dovitinib in advanced thyroid cancer

BACKGROUNDnThis phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients.nnnPATIENTS AND METHODSnPatients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety.nnnRESULTSnBetween January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancer patients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events.nnnCONCLUSIONSnDovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer.

Incidence rates and risk factors for vascular events in patients with essential thrombocythemia: a multicenter study from Korea.

BACKGROUNDnEssential thrombocythemia (ET) is classified as a Philadelphia chromosome-negative classic myeloproliferative neoplasm. ET is a clonal stem cell disorder that is often associated with JAK2 mutations and shares phenotypic and pathogenetic similarities with other myeloproliferative neoplasms. Hemorrhagic complications and arterial and venous thrombosis are common in patients with ET. The aim of this retrospective analysis was to assess the cumulative incidence rate and risk factors for thrombohemorrhagic events in patients with ET based on a multicenter study in Korea.nnnPATIENTS AND METHODSnA total of 239 patients with ET, from February 1995 to April 2011, were retrospectively analyzed from 4 Korean academic institutions. Data were collected through the review of medical records, and vascular events were confirmed by diagnostic procedures for establishing thrombosis and hemorrhagic complications.nnnRESULTSnOf the patients (median age, 61 years; median follow-up, 51.8 months), 32 (13.4%) experienced thrombohemorrhagic complications. The 10-year cumulative incidence rate showed a 20.6% incidence of thrombohemorrhagic events. In univariate analysis, the presence of JAK2 mutations, high-risk group, previous thrombohemorrhagic events, and >60 years old were shown to have higher incidences of vascular events than any other factors. In multivariate analysis, previous thrombotic events and JAK2 mutations were independent risk factors for vascular events (hazard ratio, 2.907 [95% CI, 1.142-7.406], P =.025; and 4.146 [95% CI 1.227-14.018], P = 0.022).nnnCONCLUSIONnPrevious thrombotic history and the JAK2 V617F mutation were associated with a higher 10-year cumulative incidence rate of thrombohemorrhagic events.

Comparison of therapeutic outcomes between surgical resection followed by R-CHOP and R-CHOP alone for localized primary intestinal diffuse large B-cell lymphoma.

Objectives:There is no confirmed treatment strategy for primary intestinal diffuse large B-cell lymphoma (DLBL). In this retrospective study, the purpose is to find an appropriate treatment strategy in patients with primary intestinal DLBL undergoing surgery followed by chemotherapy or chemotherapy alone. Methods:Seventy-six patients were newly diagnosed with DLBL and received treatment between March 2004 and June 2011. Forty-seven patients were treated with surgical resection followed by rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP), and 29 patients were treated with R-CHOP chemotherapy alone. Results:The characteristics of the patients were as follows: the median age was 56.5 years (range, 15 to 85 y) with a female to male ratio of 1.00:1.45. There was no significant difference in patient characteristics between the 2 groups. The estimated 3-year progression-free survival rates (PFS) and overall survival rates (OS) of surgery followed by R-CHOP (surgery/R-CHOP) and R-CHOP alone (R-CHOP) groups were 92.2% and 74.8% (P=0.009) and 94.2% and 80.7% (P=0.049), respectively. In univariate analysis, significant differences were seen in estimated PFS and OS rates when comparing Lugano stages I and II1 with II2 and IIE (P=0.006 and 0.036), low and low-intermediate risk with high-intermediate risk (P=0.004 and 0.000), and surgery/R-CHOP group with R-CHOP group (P=0.009 and 0.049), respectively. In multivariate analysis, there were no independent predictive factors for survival. Conclusions:Patients treated with surgery followed by R-CHOP seemed to have a higher survival rate than those treated with R-CHOP alone. There were no significant prognostic factors for survival, but there were possible prognostic factors such as Lugano stage, International Prognostic Index risk, and treatment modality for PFS and OS.

Herpesviridae viral infections after chemotherapy without antiviral prophylaxis in patients with malignant lymphoma: incidence and risk factors.

ObjectivesThe herpesviridae family includes, among others, herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. Herpesviridae viral infections (HVIs) can lead to serious complications in lymphoma patients undergoing chemotherapy. There is no consensus on the dose and duration of antiviral prophylaxis in these patients. We retrospectively analyzed the incidence and risk factors for HVI in lymphoma patients undergoing chemotherapy. MethodsWe reviewed the records of 266 patients who were newly diagnosed with lymphoma and received chemotherapy without acyclovir prophylaxis between June 1996 and August 2009. ResultsThe cumulative incidence rate of HVI was 20.16% for 5 years from the start of chemotherapy. Independent predictive factors for HVI in lymphoma patients were: female sex [hazard ratio (HR) 2.394; 95% confidence interval (CI): 1.245-4.607; P=0.009], cumulative dose of steroids per body surface area of at least 2500 mg/m2 (HR 7.717; 95% CI: 3.814-18.703; P<0.001), and history of neutropenic fever (HR 0.297; 95% CI: 0.150-0.588; P<0.001). ConclusionsFemale sex, high dose of steroids per body surface area, and neutropenic fever were risk factors for HVI in patients with lymphoma undergoing chemotherapy without acyclovir prophylaxis.

Bevacizumab as a second- or later-line of treatment for metastatic colorectal cancer

AIMnTo determine the efficacy of bevacizumab in patients with metastatic colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.nnnMETHODSnBetween March 2002 and June 2010, 40 patients in South Korea with MCRC who were treated with bevacizumab plus chemotherapy as a second or later-line treatment were analyzed retrospectively for their overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.nnnRESULTSnAll of the patients had progressed under prior chemotherapy without bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%) exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line, third-line and fourth- or later-line treatments, respectively. The median PFSs were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later-line treatments, respectively.nnnCONCLUSIONnIn patients with MCRC, bevacizumab combined chemotherapy may be beneficial during second- or later-line treatment.

Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study.

Purpose To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. Materials and Methods One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator’s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. Results A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea. Conclusion HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.

Herpesviridae Viral Infections following Rituximab Combined Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma

Background: Herpesviridae viral infections (HVIs) are particularly common in patients with hematologic malignancies after undergoing hematopoietic stem cell transplantation or receiving chemotherapy. However, there have been few reports on the incidence and risk factors of HVIs in diffuse large B-cell lymphoma (DLBL) patients treated with rituximab combined chemotherapy. Methods: We analyzed 270 patients who were newly diagnosed with DLBL. All of the patients had received rituximab combined chemotherapy between June 2004 and April 2010. Results: Twenty-nine patients (10.7%) developed HVI a median of 5.57 months (range 0.37–30.03) after initial chemotherapy. The estimated cumulative incidence rates of HVIs were 8.3 and 12.8% at 1 and 3 years, respectively, in all patients. Independent risk factors for HVIs were a high international prognostic index risk [p = 0.017, hazard ratio (HR) 2.633, 95% confidence interval (CI) 1.185–5.850], neutropenic fever (p = 0.023, HR 2.476, 95% CI 1.134–5.406) and a high cumulative dose of steroids (p = 0.023, HR 2.921, 95% CI 1.162–7.346). Conclusion: A high international prognostic index risk, neutropenic fever and a high cumulative dose of steroids appear to be risk factors for HVI in DLBL patients who are undergoing rituximab combined chemotherapy.