[Show abstract][Hide abstract] ABSTRACT: Targeted therapy has been proven to be one of the most effective cancer treatments. However, some endocrine disorders can occur during treatment with targeted agents. We report the case of a patient who exhibited a wax and wane pattern of hypoglycemia that was attributed to sorafenib therapy. A 32-year-old woman with metastatic hemangiopericytoma visited the emergency department in a stuporous state. Nonhyperinsulinemic hypoglycemia was diagnosed, was exacerbated shortly after sorafenib therapy, and was improved by the cessation of sorafenib with additional glucocorticoid therapy. Patients with metastatic hemangiopericytoma should be carefully monitored with particular attention to hypoglycemia when sorafenib therapy is initiated.
Endocrinology and metabolism (Seoul, Korea). 06/2014; 29(2):202-5.
[Show abstract][Hide abstract] ABSTRACT: Autophagy is a conserved catabolic process that degrades cytoplasmic proteins and organelles for recycling. The role of autophagy in tumorigenesis is controversial because autophagy can be either protective or damaging to tumor cells, and its effects may change during tumor progression. A number of cancer cell lines have been exposed to chloroquine, an anti-malarial drug, with the aim of inhibiting cell growth and inducing cell death. In addition, chloroquine inhibits a late phase of autophagy. This study was conducted to investigate the anti-cancer effect of autophagy inhibition, using chloroquine together with 5-fluorouracil (5-FU) in a colon cancer cell line. Human colon cancer DLD-1 cells were treated with 5-FU (10 μΜ) or chloroquine (100 μΜ), or a combination of both. Autophagy was evaluated by western blot analysis of microtubule-associated protein light chain3 (LC3). Proliferative activity, alterations of the cell cycle, and apoptosis were measured by MTT assays, flow cytometry, and western blotting. LC3-II protein increased after treatment with 5-FU, and chloroquine potentiated the cytotoxicity of 5-FU. MTT assays showed that 5-FU inhibited proliferation of the DLD-1 cells and that chloroquine enhanced this inhibitory effect of 5-FU. The combination of 5-FU and chloroquine induced G1 arrest, up-regulation of p27 and p53, and down-regulation of CDK2 and cyclin D1. These results suggest that chloroquine may potentiate the anti-cancer effect of 5-FU via cell cycle inhibition. Chloroquine potentiates the anti-cancer effect of 5-FU in colon cancer cells. Supplementation of conventional chemotherapy with chloroquine may provide a new cancer therapy modality.
[Show abstract][Hide abstract] ABSTRACT: Ethnic and regional differences in the epidemiology and pathological aspects of Hodgkin's lymphoma (HL) between Western and Asian patients may be associated with differences in clinical features and prognosis. We retrospectively analyzed the clinical and histopathological characteristics, therapeutic outcomes, and prognostic factors of 539 HL patients treated at 16 centers in Korea. We found that the incidence of histological subtypes of HL in Korea was similar to that in Western and other Asian countries. However, the incidence peaked between 16 and 30 years of age, unlike the bimodal age distribution seen in Western countries. In patients with stage I-IIA non-bulky disease, the complete response (CR) rate was similar between combined modality therapy and chemotherapy alone (93% vs. 84%, P = 0.44), and there was no difference in relapse-free survival (RFS) and overall survival (OS). Patients with stage I-II disease plus unfavorable factors and those with advanced-stage disease treated with combination chemotherapy regimens had an overall CR rate of 77%, with no difference between doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and non-ABVD regimens (77.2% vs. 76.8%, P = 0.95). Among those patients who achieved final CR, there was no significant difference in RFS or OS between those who achieved interim CR and PR. Only the presence of B symptoms was independently predictive of a shorter RFS. Age > 45 years, Eastern Cooperative Oncology Group 2-4, and B symptoms were independent risk factors for death. Although the incidence of HL was lower in Korea than in Western countries, the distribution of morphological subtypes, treatment outcomes, and patient prognosis were similar.
Annals of Hematology 07/2011; 91(2):223-33. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Deletion of exon 19 of the epidermal growth factor receptor (EGFR) and mutation of exon 21 are the most common EGFR mutations and predict higher response to EGFR tyrosine kinase inhibitors (TKI). Accumulating data show clinical differences in both response and survival between these two EGFR mutations. This study investigated the clinical impact of EGFR exon 19 deletion and L858R mutation by retrospectively analysing the clinical outcome of patients with advanced non-small-cell lung cancer (NSCLC) treated with EGFR TKI.
Patients harbouring EGFR exon 19 deletion or L858R mutations and who had received gefitinib or erlotinib treatment were identified. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were determined for the two groups. EGFR mutation was determined by PCR-based direct sequencing.
The study indentified 87 patients harbouring EGFR exon 19 deletion (n=61) or L858R mutation (n=26) who were treated with either gefitinib (n=83) or erlotinib (n=4). Patients with exon 19 deletion had significantly longer PFS, compared with patients with L858R mutation (9.3 vs 6.9 months, p=0.02). In a multivariate Cox regression model, EGFR exon 19 deletion was independently predictive of longer PFS (p=0.02). However, no significant differences in RR (64% vs 62%, p=0.83) and OS (17.7 vs 20.5 months, p=0.65) were observed between these two mutations.
While no significant difference in OS was observed between EGFR exon 19 deletion and L858R mutation, EGFR exon 19 deletion was predictive of longer PFS following EGFR TKI treatment in patients with advanced NSCLC.
Journal of clinical pathology 07/2011; 64(11):947-52. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptor (EGFR) mutations are associated with sensitivity to gefitinib or erlotinib in non-small cell lung cancer (NSCLC). We investigated the relationships between the two most common types of somatic EGFR mutations, exon 19 deletions and L858R mutations, and clinical outcomes of Korean NSCLC patients after treatment with gefitinib or erlotinib.
In Korean patients with NSCLC, EGFR exon 19 deletions and EGFR L858R mutation were identified from tumor specimens obtained before treatment with gefitinib or erlotinib. The response rates, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.
A total of 77 patients with either an exon 19 deletion (n = 58) or L858R mutation (n = 19) were treated with gefitinib or erlotinib. The overall response rate was 69%. Patients with an exon 19 deletion had a significantly longer PFS compared with patients with L858R mutation (9.5 vs. 7.7 months; P = 0.029). The L858R mutation was independently associated with a shorter PFS compared with an exon 19 deletion, even after adjusting for other clinical factors (hazard ratio 2.72; 95% CI 1.38-5.38). However, there were no significant differences in response rate (71 vs. 63%) and OS (21.4 vs. 30.7 months) between subjects with exon 19 deletions and L858R mutations, respectively.
In Korean NSCLC patients, EGFR exon 19 deletions are associated with longer PFS compared with EGFR L858R mutations. These observations need to be confirmed by large-scale studies of patients.
Journal of Cancer Research and Clinical Oncology 04/2011; 137(4):687-94. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic stem cell transplantation (HSCT) recipients frequently develop opportunistic infections, including paranasal sinusitis. Paranasal sinusitis in post-transplant recipients can be complicated by life-threatening infections. Accordingly, we analyzed risk factors for development of paranasal sinusitis following HSCT and reviewed our experiences for analysis of the role of management of paranasal sinusitis prior to HSCT. A retrospective review was performed for patients who had received HSCT at Samsung Medical Center (Seoul, South Korea) from 1996 to 2003. A total of 252 patients were analyzed. While 23 patients (9.1%) had sinusitis prior to HSCT, its occurrence rate increased to 15.9% after HSCT. Patients with pre-HSCT sinusitis showed a high occurrence rate of post-HSCT sinusitis (34.8 vs. 14.0%, p = 0.015). However, when pre-HSCT radiological abnormality alone was compared to no evidence of sinusitis prior to HSCT, there was no significant difference in the occurrence rates of post-HSCT sinusitis (15.6 vs. 12.8%, p = 0.541). Although statistical significance was not demonstrated, the occurrence rate of post-HSCT sinusitis was relatively low in patients who received autologous HSCT compared to those who received allogeneic HSCT (11.3 vs. 20.3%, p = 0.060). Use of total body irradiation and presence of graft-versus-host disease did not correlate with development of post-HSCT sinusitis. Compared to the observation group, occurrence of post-HSCT sinusitis showed a slight reduction with medical or surgical intervention targeting radiological abnormalities of the paranasal sinuses (10.0 vs. 25.0%, p = 0.057). In conclusion, pre-HSCT sinusitis and allogeneic HSCT are associated with development of post-HSCT sinusitis. Although asymptomatic radiological abnormalities of the sinus do not increase the risk of post-HSCT sinusitis, optimal treatment prior to HSCT tends to decrease the risk of post-HSCT sinusitis.
International journal of hematology 03/2011; 93(3):383-8. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gefitinib and erlotinib are commonly used for salvage therapy in patients with nonsmall cell lung cancer (NSCLC) who have progressed on prior therapies. Although both agents have similar structure and have demonstrated efficacy in NSCLC, gefitinib and erlotinib have not been directly compared in terms of efficacy and other clinical outcomes in patients with NSCLC who have failed prior chemotherapy. This prompted us to analyze the clinical outcomes between gefitinib-treated and erlotinib-treated patients with metastatic or recurrent NSCLC.
A total of 467 patients with metastatic or recurrent NSCLC who had progressed on prior therapies and received gefitinib or erlotinib therapy between January 2006 and December 2008 were retrospectively reviewed. By using a matched-pair case-control study design, 171 pairs of gefitinib-treated and erlotinib-treated patients were matched according to sex, Eastern Cooperative Oncology Group (ECOG) performance status, histologic type, and smoking history.
The median age of all patients was 58 years (range, 20-85 years), and the median ECOG performance status was 1 (range, 0-3). Of 342 patients, 294 (86%) received an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor as second-line or third-line therapy, whereas the remaining 14% had received >2 prior chemotherapy regimens before starting EGFR TK inhibitor therapy. The confirmed overall response rate was 35.1%, and the disease control rate was 64%. With 13.2 months of follow-up, the median overall survival (OS) for the total 342 patients was 12.4 months (95% confidence interval [95% CI], 10.66-14.14 months), and the median progression-free survival (PFS) was 3.2 months (95% CI, 2.65-3.75 months). The overall response rates and disease control rates in the gefitinib-treated and erlotinib-treated groups were 38% versus 32.2% (P = .273) and 63.2% versus 64.9%, respectively (P = .677). There was no statistically significant difference noted with regard to OS (median, 12.6 vs 12.1 months; P = 0.99) and PFS (median, 4.6 vs 2.7 months; P = .06) between the gefitinib-treated and erlotinib-treated groups.
This retrospective analysis shows that gefitinib and erlotinib appear to have similar antitumor activity in terms of response rate and OS in pretreated patients with metastatic or recurrent NSCLC. Further prospective studies are warranted to elucidate any potential differences in toxicity and in dose intensity between gefitinib- and erlotinib-treated patients.
Cancer 06/2010; 116(12):3025-33. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy.
A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei.
Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%).
In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.
Cancer Research and Treatment 06/2010; 42(2):101-6. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphoplasmacytic lymphoma (LPL) constitutes less than 5% of all non-Hodgkin lymphomas, and little is known about clinical features and treatment outcomes for patients with LPL in East Asia. In this study, we summarize our experiences managing patients diagnosed with LPL in Korea. A retrospective analysis was performed using data for 22 patients with LPL diagnosed at Samsung Medical Center. LPL was more common among males (77.3%), with a median age of diagnosis of 63 years (range 26-86). The most common presenting symptom was fatigue related to anemia (59.1%), and the bone marrow was commonly involved at diagnosis (90.9%). IgM paraproteinemia was found in 15 patients, and only one patient had anti-hepatitis C virus. Although some patients could be observed without treatment, the majority of patients required systemic treatment. Chlorambucil alone and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like combination chemotherapy was frequently used as a first-line treatment, and a fludarabine-based regimen was commonly used as salvage therapy. However, responses to those treatments were not satisfactory. Even patients who could be monitored without therapy became refractory to salvage therapies once their disease progressed. Eight patients died due to disease progression, and the median overall survival was 70.8 months (95% CI: 31.4-109.2 months). This study describes the clinical features and treatment outcome of LPL in Korea. The treatment approach was too heterogeneous to draw firm conclusions, however, and treatment recommendations in the future should utilize a uniform treatment strategy.
Annals of Hematology 05/2010; 89(10):1011-8. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The addition of rituximab to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of rituximab (R-CHOP) is still not determined in primary mediastinal large B-cell lymphoma (PMBCL), a subtype of DLBCL, especially in Asian patients. Thus, we analyzed the treatment outcome of PMBCL patients (n = 21) treated with R-CHOP and compared it with the historical group treated with CHOP (n = 14). The rate of complete response for R-CHOP was higher than that of CHOP (17/21, 81.0% vs. 8/14, 57.2%), although the difference was not statistically significant (P = 0.151). The number of patients with disease progression or relapse was higher in the CHOP group (6/14, 42.9%) than the R-CHOP group (2/21, 9.5%). Thus, patients treated with R-CHOP had higher 2-year progression-free survival (79.0%) than those treated with CHOP (50.0%, P = 0.043). Although the 2-year overall survival of the R-CHOP was also superior to that of the CHOP group (82.7% vs. 57.1%), this survival benefit did not reach statistical significance (P = 0.081). In conclusion, our comparison suggests that R-CHOP may increase response and reduce relapse resulting in prolongation of progression-free survival of patients with PMBCL.
International journal of hematology 03/2010; 91(3):456-63. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prospective studies have implied that maintenance therapy for non-small cell lung cancer (NSCLC) has its effect by giving active drugs earlier to patients who otherwise die without receiving second-line therapy. The purpose of this study was to select patients with NSCLC who could most benefit from maintenance therapy, by evaluating which patients would be less likely to receive second-line therapy.
Clinicopathologic data of patients with advanced NSCLC who received four cycles of first-line chemotherapy followed by time-off therapy and eventual disease progression or death were reviewed retrospectively. Patients were grouped into ones with first-line therapy only or ones with more than first-line therapy. Clinical characteristics between the two groups were compared.
A total of 271 patients were eligible for analysis, and 39 patients (14.4%) received only first-line therapy. Patients significantly more likely to receive only first-line therapy had performance status of two or three after first-line therapy, large volume of initial target lesions (sum of long diameters >or=70 mm), or smaller decrease in target lesions (decrease <20%) after first-line therapy. Median overall survival of the 143 patients (52.8%) with at least one of these characteristics (16.3 months) was significantly shorter than that of patients without any of these characteristics (23.5 months, p = 0.007).
Maintenance therapy may be of greater benefit to patients with NSCLC who have clinical characteristics including poor performance status after first-line therapy, large initial target lesions, or smaller decrease in target lesions after first-line therapy.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2010; 5(4):540-5. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Renin-angiotensin system (RAS) blockades, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well accepted for the cardiorenal-protective benefits added to antihypertensive effects in chronic kidney diseases (CKD), but associated with an increased risk of hyperkalaemia. However, few studies have investigated the effect of RAS blockades on serum potassium in dialysis patients.
Hyperkalaemia associated with RAS blockades by ACEI and/or ARB was evaluated in 69 patients on maintenance haemodialysis, who underwent a three-period crossover study in four groups (no exposure to RAS blockades, ACEI or ARB alone and ACEI plus ARB treatments), lasting one month in each period.
Sixty-two patients completed this prospective 3-month study, and no one stopped the study because of the development of hyperkalaemia and/or complications. Mean serum K was similar among the four periods (no exposure, 5.54+/-0.67 mmol/l; ACEI alone, 5.54+/-0.75 mmol/l; ARB alone, 5.50+/-0.66 mmol/l; ACEI+ARB combination, 5.42+/-0.66 mmol/l) and was also equal when compared between the two groups with and without exposure to RAS blockades (5.48+/-0.68 vs 5.54+/-0.67 mmol/l, P=NS). The incidence of severe hyperkalaemic episodes (>6.0 mmol/l) upon monthly predialysis serum K determination was 25.8% with no exposure to RAS blockades, 29.8% for ACEI alone, 19.6% for ARB alone and 17.7% for ACEI+ARB combination without statistically significant differences among the four periods (P=NS). Among covariables, the degree of Kt/V, intakes of other medications interfering with potassium homeostasis and diabetes mellitus did not result in any significant hyperkalaemic changes during the 3-month study period except anuric patients compared with non-anuric patients (5.58+/-0.69 vs 5.19+/-0.65 mmol/l, P<0.001).
Neither monotherapy (ACEI or ARB) nor combination therapy (ACEI plus ARB) is associated with the additional risk of hyperkalaemia in patients on maintenance haemodialysis. However, those patients with anuria on RAS blockades warrant the cautious monitoring of serum K to prevent hyperkalaemia.
[Show abstract][Hide abstract] ABSTRACT: Idiopathic thrombocytopenic purpura (ITP) is a condition that often develops in young women and, consequently, physicians should frequently manage and monitor pregnant patients with this disorder.
We reviewed the charts of 30 women with chronic ITP delivered in 31 pregnancies from January 1995 to December 2003.
Fifteen patients were diagnosed with ITP before pregnancy and sixteen patients were diagnosed during pregnancy. The mean platelet counts before pregnancy, during pregnancy, and at delivery were 70,040/mm3, 83,960/mm3, and 62,680/mm3, respectively. The symptoms of hemostatic impairment were not noted in most of the pregnancies (77%, 24/31). During pregnancy and at delivery, most of the women (61%, 19/31) received various kinds of treatment to raise platelet counts. At delivery, the most commonly used therapy was platelet transfusion (48.4%, 15/31). Seven pregnancies (22.6%) were treated with corticosteroids during pregnancy and at delivery. Five pregnancies (16.1%) were treated with IV IgG during pregnancy and at delivery. Fifteen deliveries (51.7%) were performed by cesarean section and fourteen (48.3%) with vaginal delivery. Bleeding was uncommon at delivery. There were no cases of infants with any clinical signs of hemorrhage.
Our current results suggest that ITP in pregnancy can proceed safely with low hemorrhagic risk in both infants and mothers, and that mothers with ITP can deliver healthy infants without serious hemorrhagic complications.
The Korean Journal of Internal Medicine 07/2005; 20(2):129-34.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer.
Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m(2) on days 1 and 15; 5-FU 400 mg/m(2) bolus IV with 600 mg/m(2) by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks.
The median age of the 24 was 57.5 years (range, 38 approximately 69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3 approximately 44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7 approximately 26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity.
The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.
Cancer Research and Treatment 08/2004; 36(4):235-9. · 1.96 Impact Factor