Publications by authors named "Suee Lee"

80 Publications

Prognostic effects of cytokine levels on patients treated with taxane and zoledronic acid for metastatic breast cancer in bone (BEAT-ZO) (KCSG BR 10-13).

Cytokine 2021 Jun 23;142:155487. Epub 2021 Mar 23.

Korea University Anam Hospital, Seoul, Republic of Korea.

Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-β1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-β1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-β1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-β1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2021.155487DOI Listing
June 2021

Relationship between heavy metal exposure and type 2 diabetes: a large-scale retrospective cohort study using occupational health examinations.

BMJ Open 2021 Mar 4;11(3):e039541. Epub 2021 Mar 4.

Internal Medicine, Dong-A University Medical Center, Busan, The Republic of Korea

Objectives: To investigate the associations between heavy metal exposure and serum ferritin levels, physical measurements and type 2 diabetes mellitus (DM).

Design: A retrospective cohort study.

Setting: Changwon, the location of this study, is a Korean representative industrial city. Data were obtained from medical check-ups between 2002 and 2018.

Participants: A total of 34 814 male subjects were included. Of them, 1035 subjects with lead exposure, 200 subjects with cadmium exposure and the 33 579 remaining were assigned to cohort A, cohort B and the control cohort, respectively. Data including personal history of alcohol and smoking, age, height, weight, the follow-up duration, haemoglobin A1c (HbA1c), fasting blood sugar (FBS), ferritin levels, and lead and cadmium levels within 1 year after exposure were collected.

Primary Outcome Measure: In subjects without diabetes, changes in FBS and HbA1c were analysed through repeated tests at intervals of 1 year or longer after the occupational exposure to heavy metals.

Results: In Cohort A, DM was diagnosed in 33 subjects. There was a significant difference in lead concentrations between the subjects diagnosed with DM and those without DM during the follow-up period (3.94±2.92 mg/dL vs 2.81±2.03 mg/dL, p=0.002). Simple exposure to heavy metals (lead and cadmium) was not associated with DM in Cox regression models (lead exposure (HR) 1.01, 95% CI: 0.58 to 1.77, p 0.971; cadmium exposure HR 1.48, 95% CI: 0.61 to 3.55, p=0.385). Annual changes in FBS according to lead concentration at the beginning of exposure showed a positive correlation (r=0.072, p=0.032).

Conclusion: Our findings demonstrated that simple occupational exposure to heavy metals lead and cadmium was not associated with the incidence of DM. However, lead concentrations at the beginning of the exposure might be an indicator of DM and glucose elevations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-039541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934714PMC
March 2021

rhEGF Treatment Improves EGFR Inhibitor-Induced Skin Barrier and Immune Defects.

Cancers (Basel) 2020 Oct 25;12(11). Epub 2020 Oct 25.

Department of Pathology, Dong-A University College of Medicine, Busan 49201, Korea.

The mechanisms of epidermal growth factor (EGF) affecting EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF's positive effects. Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). As a result, rhEGF increased EGFR and pEGFR expression. Furthermore, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. In addition, rhEGF bound to EGFR after than cetuximab, but cetuximab bound to EGFR more strongly than rhEGF. Moreover, expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRI-treated tissue. However, in rhEGF and EGFRI co-treated tissue, those expressions were increased. Expression of IL-1α, IL-8, and TNF-α was increased by EGFRIs and down-regulated by rhEGF. Furthermore, hBD-2 and hBD-3 protein expressions were inhibited by cetuximab or gefitinib treatment, and those decrements were increased by rhEGF treatment. In patients' tissue evaluation, compared with controls, patients' Ki-67 and EGFR expression were decreased ( = 0.015, = 0.001). Patients' IL-17 and TNF-α expression intensity was higher than that of the control group ( = 0.038, = 0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely, patients' proportions of IL-17 and TNF-α were decreased to low stain level. In conclusion, treatment of rhEGF improved EGFRI-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692663PMC
October 2020

Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing.

Oncol Lett 2020 Nov 8;20(5):205. Epub 2020 Sep 8.

Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea.

Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma that can be classified as a mucosal-associated lymphoid tissue (MALT) lymphoma. Recently, second-generation or next-generation sequencing (NGS), which allows simultaneous sequencing of hundreds to billions of DNA strands, has been a focus of attention and is rapidly being adopted in various fields. In the present study, paraffin-embedded tissue samples of gastric MALT lymphoma (n=1) and small intestine MALT lymphoma (n=4) were selected, and DNA was extracted from the tissue samples. After performing quality control, NGS was performed using HemaSCAN™, a custom panel of 426 genes, including essential blood cancer genes. NGS revealed single nucleotide variations (SNVs), short insertions and deletions (InDels) and copy number variations (CNVs). These genomic variants were reported as annotated, known or novel variants. An annotated variant, an erb-b2 receptor tyrosine kinase 2 gene amplification, was observed in one patient. Known and novel variants, including SNVs of SET binding protein 6 (SETBP6), Runt-related transcription factor 1 and Kelch-like ECH-associated protein 1 genes, InDel of the marker of proliferation Ki-67 gene, and CNVs of the zinc finger protein 703 and NOTCH1 genes, were observed in ≥2 patients. Additionally, InDels with frameshift mutations were identified in the B-cell lymphoma/leukemia 10, DEAD-box helicase 3 X-linked, forkhead box O3 and mucin 2, oligomeric mucus/gel-forming genes in one patient. Since few NGS studies have been performed on MALT lymphoma, the current results were unable to determine if the different mutations that were identified are 'actionable' (that is, potentially responsive to a targeted therapy) Further studies are required to determine the associations between genetic mutations and the development of MALT lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2020.12068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491050PMC
November 2020

Randomised Phase 2 study of lapatinib and vinorelbine vs vinorelbine in patients with HER2 + metastatic breast cancer after lapatinib and trastuzumab treatment (KCSG BR11-16).

Br J Cancer 2019 12 6;121(12):985-990. Epub 2019 Nov 6.

Center for Breast Cancer, Research Institute, National Cancer Center, Goyang, Korea.

Background: The continuum of anti-HER2 agents is a standard treatment of HER2 + metastatic breast cancer (MBC). This study evaluated the efficacy of lapatinib plus vinorelbine in patients progressed on both trastuzumab and lapatinib treatments.

Methods: A total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n = 75; lapatinib, 1000 mg daily; vinorelbine 20 mg/m D1, D8 q3w) or vinorelbine (V) (n = 74; 30 mg/m D1, D8 q3w). The primary endpoint was progression-free survival (PFS) rate at 18 weeks.

Results: The median number of previous anti-HER2 therapies was 2 (range 2-5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (45.9% vs 38.9%, p = 0.40). ORR was 19.7% in LV arm, and 16.9% in V arm (p = 0.88). PFS and OS did not differ between two arms (LV vs V; median PFS, 16 vs 12 weeks, HR = 0.86, 95% CI 0.61-1.22; median OS, 15.0 vs 18.9 months, HR = 1.07, 95% CI 0.72-1.58). Toxicity profiles were similar in both arms and all were manageable.

Conclusions: Lapatinib plus vinorelbine treatment was tolerable; however, it failed to demonstrate the clinical benefits over vinorelbine alone in patients with HER2 + MBC after progression on both trastuzumab and lapatinib.

Clinical Trial Registration: ClinicalTrials.gov number NCT01730677.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-019-0618-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964682PMC
December 2019

Phase II study of R-CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study.

Cancer Commun (Lond) 2019 10 16;39(1):58. Epub 2019 Oct 16.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation.

Methods: Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m), cyclophosphamide (750 mg/m), and vincristine (1.4 mg/m; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety.

Results: 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%).

Conclusion: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40880-019-0403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796378PMC
October 2019

A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities.

Oncologist 2020 01 6;25(1):e186-e193. Epub 2019 Sep 6.

Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea.

Background: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs).

Materials And Methods: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily.

Results: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm.

Conclusion: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964120PMC
January 2020

Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea.

Cancer Res Treat 2020 Jan 12;52(1):277-283. Epub 2019 Jul 12.

Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.

Purpose: The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage.

Materials And Methods: Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected.

Results: Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence.

Conclusion: Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2019.292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962489PMC
January 2020

The Glasgow Prognostic Score is a significant predictor of peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy and comparable with PTCL prognostic scores.

Int J Hematol 2019 Oct 27;110(4):438-446. Epub 2019 Jun 27.

Department of Internal Medicine, Dong-A University College of Medicine, 26 Daeshingongwon-ro, Seo-gu, Busan, 49201, South Korea.

The Glasgow Prognostic Score (GPS) serves a prognostic role in several lymphomas. The objectives of the present study were to determine whether GPS predicts clinical outcomes and to compare the utility of four prognostic scores, including GPS, in patients diagnosed with peripheral T-cell lymphoma (PTCL). We selected for this retrospective study 96 patients consecutively diagnosed with PTCL according to the World Health Organization classification from January 2002 to February 2013 and followed up in five different institutions. Low GPS was a good prognostic biomarker of progression-free survival (PFS, P = 0.030) and overall survival (OS, P = 0.013). Estimated 3-year OS rates (low-risk vs. intermediate- or high-risk) by the International Prognostic Index (IPI), the Prognostic Index for T-cell lymphoma (PIT), the International Peripheral T-cell Lymphoma Project (IPTCLP) score, and GPS were 83% vs. 44% (P < 0.001), 68% vs. 37% (P = 0.004), 71% vs. 26% (P < 0.001) and 68% vs. 51% (P = 0.031), respectively. These results indicate that GPS has prognostic value for PTCL. In addition, all four prognostic scores demonstrate their usefulness in assessing PTCL outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-019-02693-zDOI Listing
October 2019

BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy.

Cancer Res Treat 2019 Oct 4;51(4):1527-1539. Epub 2019 Jun 4.

Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Purpose: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents.

Materials And Methods: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.

Results: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.

Conclusion: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2018.598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790855PMC
October 2019

Safety and efficacy of trastuzumab administered as a 30-min infusion in patients with HER2-positive advanced gastric cancer.

Cancer Chemother Pharmacol 2019 03 8;83(3):501-508. Epub 2018 Dec 8.

CELLTRION Healthcare Co. Ltd, Incheon, Republic of Korea.

Purpose: To investigate the safety and efficacy of 30-min maintenance infusions of trastuzumab in advanced gastric cancer positive for human epidermal growth factor receptor 2 (HER2).

Methods: This was a retrospective study conducted across five Korean hospitals in patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with first-line, 3-weekly trastuzumab plus chemotherapy. The first dose of trastuzumab (8 mg/kg) was administered as a 90-min infusion, with all subsequent maintenance infusions (6 mg/kg) given over 30 min. The primary aim was to investigate infusion-related reactions and cardiac events with 30-min infusions of trastuzumab. Objective response rate, progression-free survival, and overall survival were secondary endpoints.

Results: The study included 128 patients (efficacy population), of whom 123 received both induction and maintenance infusions and formed the safety population. The median age was 63 years; 80% were presenting for the first time with metastatic disease, and 94% were treated with trastuzumab plus capecitabine/cisplatin. Infusion-related reactions were observed in 32 of 123 patients (26%). There were no cardiac events. The most frequent adverse events were anorexia and nausea, followed by vomiting, fatigue, mucositis, sensory neuropathy, and hand-foot syndrome. Most events were grade 1-2 and were manageable. No patient discontinued study treatment due to adverse events. The objective response rate was 63%, and included 6 complete responses.

Conclusions: Trastuzumab 30-min maintenance infusions were well tolerated with a good safety profile, and resulted in sustained efficacy in patients with HER2-positive advanced gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-018-3753-yDOI Listing
March 2019

Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01).

Cancer Res Treat 2019 Jan 14;51(1):43-52. Epub 2018 Feb 14.

Division of Internal Medicine, Center for Breast Cancer, National Cancer Center, Goyang, Korea.

Purpose: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).

Materials And Methods: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.

Results: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.

Conclusion: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2017.562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333992PMC
January 2019

Clinical significance of coagulation factors in operable colorectal cancer.

Oncol Lett 2017 Jun 20;13(6):4669-4674. Epub 2017 Apr 20.

Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea.

Abnormal hemostasis in cancer patients has prev iously been studied. The primary objective of the present study was to evaluate the association between preoperative hemostasis markers and clinicopathological parameters, and to identify a hemostasis marker affecting survival in patients following curative resection for colorectal cancer. A total of 170 patients who underwent curative surgery for colorectal carcinoma were evaluated. Preoperative coagulation tests included platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and fibrinogen degradation product (FDP). The clinicopathological variables, including age, gender, tumor location (rectum/colon), tumor size (≥5 cm vs. <5 cm), depth of tumor invasion, lymph node metastasis, stage, lymphovascular invasion, margin involvement and histological differentiation were analyzed. The median age of analyzed patients was 63 years (range, 28-84). The male to female ratio was 62:38. Increased levels of plasma fibrinogen, PT and platelet count (PLT) were associated with larger tumor size (P<0.001, P=0.015 and P=0.002, respectively). Increased plasma fibrinogen levels were significantly associated with depth of tumor invasion and stage (P=0.014 and P=0.048, respectively). Increased plasma D-dimer and FDP levels were significantly associated with tumor node metastasis stage (P=0.031 and P=0.002, respectively). Prolonged PT level (≥11.7 sec), hyper-fibrinogenemia (≥327 mg/dl), high D-dimer level (≥1.3 µg/ml) and increased FDP level (≥2.7 µg/ml) were the prognostic factors associated with shorter survival. Preoperative plasma fibrinogen level was significantly associated with tumor size and depth of tumor invasion. Preoperative plasma prolonged PT level, hyperfibrinogenemia, high D-dimer level and increased FDP level may function as hemostasis markers that predict overall survival in operable patients with colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2017.6058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452961PMC
June 2017

Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study.

Cancer Res Treat 2018 Apr 22;50(2):488-494. Epub 2017 May 22.

Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.

Materials And Methods: Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).

Results: A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.

Conclusion: In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2016.584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912146PMC
April 2018

Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic Breast Cancer: Korean Multi-center Phase IV Clinical Study Results.

Cancer Res Treat 2017 Apr 3;49(2):423-429. Epub 2016 Aug 3.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC), who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials.

Materials And Methods: In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease.

Results: A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively.

Conclusion: This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2016.191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398406PMC
April 2017

Retrospective analysis of palliative chemotherapy for the patients with bladder adenocarcinoma: Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee.

Korean J Intern Med 2018 03 6;33(2):383-390. Epub 2016 Apr 6.

Dong-A University Hospital, Busan, Korea.

Background/aims: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma.

Methods: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up.

Results: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS ( = 0.024 and = 0.046, respectively).

Conclusions: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2015.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840579PMC
March 2018

Clinicopathologic significance of tumor microenvironment CD11c, and FOXP3 expression in diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy.

Korean J Intern Med 2017 Mar 11;32(2):335-344. Epub 2016 Mar 11.

Immune-Network Pioneer Research Center, Dong-A University College of Medicine, Busan, Korea.

Background/aims: CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors' microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy.

Methods: The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors' microenvironment were evaluated using an immunohistochemistry (IHC).

Results: CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival ( = 0.019) and overall survival ( = 0.039) between the two groups.

Conclusions: We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2015.161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339461PMC
March 2017

Malignant Adenomyoepithelioma of the Breast and Responsiveness to Eribulin.

J Breast Cancer 2015 Dec 23;18(4):400-3. Epub 2015 Dec 23.

Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.

Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4048/jbc.2015.18.4.400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705093PMC
December 2015

Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia.

Korean J Intern Med 2015 Nov 30;30(6):884-90. Epub 2015 Oct 30.

Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.

Background/aims: This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis.

Methods: A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012.

Results: A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS).

Conclusions: Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2015.30.6.884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642018PMC
November 2015

Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06).

Oncologist 2015 Nov 30;20(11):1312-9. Epub 2015 Sep 30.

Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Background: KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications.

Methods: We conducted a phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily. The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population.

Results: Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2 (4.8%) patients had KIT mutations, KIT amplifications, and both KIT mutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%-28.0%) and a disease control rate of 57.1% (95% CI: 42.1%-72.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KIT mutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only.

Conclusion: Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.

Implications For Practice: KIT aberration can be detected in a subset of metastatic melanoma patients. This phase II trial showed that nilotinib demonstrates durable response in a subset of patients with KIT mutations. The safety profile was very tolerable. This study suggests that a KIT inhibitor may benefit a small subset of metastatic melanoma patients with KIT mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2015-0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718426PMC
November 2015

A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial.

Leuk Lymphoma 2016 16;57(6):1406-12. Epub 2015 Nov 16.

h Department of Oncology , Asan Medical Center, University of Ulsan College of Medicine , Seoul , Korea ;

Overall, more than 50% of marginal zone lymphoma (MZL) patients experience a relapse within 10 years. This phase II trial was conducted to assess the efficacy and safety of oxaliplatin-prednisone (Ox-P) chemotherapy for patients with relapsed or refractory MZL. Patients received oxaliplatin 130 mg/m(2) on day 1 and prednisone 100 mg/day on days 1-5 of each cycle. A total of 38 patients were enrolled. The median age of the 34 (16 males, 18 females) evaluated patients was 53 (range = 27-74) years. There were seven complete responses (20.6%) and 15 partial responses (44.1%) (Overall response rate = 64.7%). No treatment-related deaths occurred. The median progression-free survival was 14.2 months (95% CI = 2.1-26.3 months); 3-year overall survival rate was 77.7%. Thus, salvage Ox-P chemotherapy for patients with relapsed or refractory MZL at the stated dosage and schedule showed moderate clinical activity and was considerable in very few selected patients (NCT01068392).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428194.2015.1099650DOI Listing
January 2017

Clinical Significance of Peroxisome Proliferator-Activated Receptor γ and TRAP220 in Patients with Operable Colorectal Cancer.

Cancer Res Treat 2016 Jan 23;48(1):198-207. Epub 2015 Jun 23.

Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.

Purpose: The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARγ or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC).

Materials And Methods: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARγ and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated.

Results: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARγ and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARγ positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARγ and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048).

Conclusion: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARγ and TRAP220 represents a biomarker for good prognosis in CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2015.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720060PMC
January 2016

Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects.

Support Care Cancer 2016 Jan 4;24(1):301-309. Epub 2015 Jun 4.

Department of Internal Medicine, Dong-A University Hospital, Busan, Republic of Korea.

Purpose: The efficacy of erlotinib, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer (PC). In the present study, we evaluated the effect of epidermal growth factor (EGF) ointment on erlotinib-related skin effects (ERSEs).

Methods: This was an open-label, non-comparative, multicenter, phase II trial. The patients included those diagnosed with NSCLC or PC who were treated with erlotinib. The effectiveness of the ointment was defined as follows: (1) grade 2, 3, or 4 ERSEs downgraded to ≤ grade 1 or (2) grade 3 or 4 ERSEs downgraded to grade 2 and persisted for at least 2 weeks.

Results: Fifty-two patients from seven institutes in Korea were enrolled with informed consent. The final assessment included 46 patients (30 males, 16 females). According to the definition of effectiveness, the EGF ointment was effective in 36 (69.2%) intention to treat patients. There were no statistically significant differences in the effectiveness of the EGF ointment by gender (p = 0.465), age (p = 0.547), tumor type (p = 0.085), erlotinib dosage (p = 0.117), and number of prior chemotherapy sessions (p = 0.547). The grading for the average National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) rating of rash/acne and itching improved from 2.02 ± 0.83 to 1.13 ± 0.89 and 1.52 ± 0.84 to 0.67 ± 0.90, respectively (p < 0.001). The most common reason for discontinuing the study was progression of cancer (37%).

Conclusions: Based on the results, the EGF ointment is effective for ERSEs, regardless of gender, age, type of tumor, and dosage of erlotinib. The EGF ointment evenly improved all kinds of symptoms of ERSEs.

Clinical Trial Registration No: ClinicalTrials.gov identifier: NCT01593995.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-015-2783-9DOI Listing
January 2016

Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer.

Cancer Chemother Pharmacol 2015 Apr 13;75(4):757-62. Epub 2015 Feb 13.

Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 224 Heukseok-dong, Dongjak-gu, Seoul, 156-755, Korea.

Purpose: We conducted a phase II trial of 5-fluorouracil and oxaliplatin combination chemotherapy as a second-line treatment in unresectable/metastatic biliary tract cancer patients who had failed gemcitabine-based chemotherapy.

Methods: Patients treated with gemcitabine-based palliative treatment were enrolled in this study. Patients were received modified FOLFOX3 (mFOLFOX3) consists of oxaliplatin 85 mg/m(2) (day 1) and leucovorin 30 mg (days 1, 2) followed by 5-fluorouracil 1,500 mg/m(2) (days 1, 2) every 2 weeks.

Results: Between March 2010 and June 2012, a total of 30 patients were enrolled in this study. Twenty-eight patients were measurable for treatment response. One achieved complete response, and one a partial response was observed. Overall response rate was 7.1% (95% confidence interval 0.9-23.5%). The median progression-free survival was 1.6 months, and the median overall survival was 4.4 months. Grade 3-4 hematologic toxicities included neutropenia (6.7%) and thrombocytopenia (3.4%). The most common non-hematologic toxicity was neuropathy (22.2%). However, the most common grade 3-4 non-hematologic toxicity was hyperbilirubinemia (5.0%). There was one treatment-related death due to neutropenic infection.

Conclusion: mFOLFOX3 as a second-line regimen has modest effect and tolerable toxicity in unresectable/metastatic biliary tract cancer patients who have been treated previously via gemcitabine-based chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-015-2691-1DOI Listing
April 2015

DNA ligase4 as a prognostic marker in nasopharyngeal cancer patients treated with radiotherapy.

Asian Pac J Cancer Prev 2014 ;15(24):10985-9

Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea E-mail :

Background: The capability for DNA double-strand breaks (DSBs) repair is crucial for inherent radiosensitivity of tumor and normal cells. We have investigated the clinicopathologic significance of DNA repair gene expression in nasopharyngeal (NP) carcinoma.

Materials And Methods: A total of 65 NP cancer patients who received radiotherapy were included. The immunopositivity to Ku 70, DNA-PKcs, MRN, RAD50, XRCC4, and LIG4 were examined in all tumor tissues.

Results: The patients comprised 42 males and 23 females, with a median age of 56 years (range, 18-84). The expression levels of RAD50 (0,+1,+2,+3) were 27.7%, 32.3%, 21.5%, and 18.5%. LIG4 (±) were 43.1% and 56.9% respectively. The 5-year OS rate of patients with LIG4 (±) were 90% and 67.9%, respectively (p=0.035). The 5-year TTP rate of patients with LIG4 (±) were 75.9%, 55.5%, respectively (P=0.039).

Conclusions: Our results suggest the possibility of predicting the radiosensitivity of NP cancer by performing immunohistochemical analysis of LIG4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7314/apjcp.2014.15.24.10985DOI Listing
October 2015

Prognostic and Clinicopathologic Associations of BRAF Mutation in Primary Acral Lentiginous Melanoma in Korean Patients: A Preliminary Study.

Ann Dermatol 2014 Apr 30;26(2):195-202. Epub 2014 Apr 30.

Department of Dermatology, Dong-A University College of Medicine, Busan, Korea.

Background: In the majority of melanomas, the RAS/RAF/MEK/ERK signaling pathway is constitutively activated, due to oncogenic mutations in the BRAF and NRAS genes. The BRAF mutation has been mainly described in Caucasian melanomas. However, there is a lack of study evaluating the status, and the clinical significance, of BRAF mutation in the Asian population.

Objective: This study was aimed to determine the frequency of BRAF mutation, and to evaluate the correlation of BRAF status with clinicopathologic features and outcomes, in Korean primary acral lentiginous melanoma (ALM) patients.

Methods: ALM samples (n=36) were analyzed for the BRAF V600E mutation, by dual-priming oligonucleotide (DPO) based real-time polymerase chain reaction. The clinicopathologic features and prognosis of the patients were analyzed with BRAF mutation status.

Results: The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations were not associated with clinicopathologic features, except for the age factor. All of the BRAF-mutant patients survived without recurrence or metastasis, and have a better clinical outcome than BRAF wild-type patients.

Conclusion: In Korean primary ALM, a low frequency of BRAF mutation was shown; and BRAF mutation presented with a favorable prognosis. These results indicate that other distinctive genetic mechanisms may have more important roles in the development and progression of disease. Further multicenter study with large sample size is firmly needed, to confirm the results of our preliminary study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5021/ad.2014.26.2.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037672PMC
April 2014

Long-term survival analysis and clinical follow-up in acral lentiginous malignant melanoma undergoing sentinel lymph node biopsy in korean patients.

Ann Dermatol 2014 Apr 30;26(2):177-83. Epub 2014 Apr 30.

Department of Dermatology, Dong-A University College of Medicine, Busan, Korea.

Background: In cutaneous malignant melanoma (MM) with clinically uninvolved regional lymph nodes, sentinel lymph node (SLN) status is the most powerful indicator of both overall survival (OS) and disease-free survival (DFS). However, no studies on the long-term survival and clinical follow-up of Korean patients with acral lentiginous MM (ALM) undergoing SLN biopsy (SLNB) have been published.

Objective: The purpose of this study was to investigate the clinical prognosis and long-term survival of Korean patients with ALM according to SLN status.

Methods: Thirty-four ALM patients undergoing SLNB were included in this study. We evaluated clinical and histopathological follow-up data such as the stage of disease, treatment, recurrence, and metastasis, and analyzed OS and DFS according to SLN status.

Results: The median follow-up time was 60.5 months (range 3~127 months). Positive SLNs were noted in 14 patients (41.2%). Patients with negative SLNs had better OS and DFS than those with positive SLNs (p<0.05). Increased Breslow thickness was associated with short OS and DFS (p<0.05), and female patients showed better DFS than male patients (p<0.05).

Conclusion: To our knowledge, this is the first study on the long-term survival and clinical follow-up of patients undergoing SLNB for ALM in Korea. Our findings show that SLN status is an important prognostic factor for predicting OS and DFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5021/ad.2014.26.2.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037669PMC
April 2014

Prognostic significance of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in biliary tract cancer patients receiving adjuvant 5-fluorouracil-based chemotherapy.

Mol Clin Oncol 2013 Nov 6;1(6):987-994. Epub 2013 Aug 6.

Department of Surgery, Haeundae Paik Hospital, College of Medicine, Inje University;

Biliary tract cancer (BTC) is a relatively uncommon type of cancer, accounting for ∼4% of the malignant neoplasms of the gastrointestinal tract. The aim of this study was to determine whether the expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) predict clinical outcome in BTC patients treated with adjuvant 5-fluorouracil (5-FU)-based chemotherapy. TS and TP expression were found to be significantly correlated with cancer location (P=0.044 and 0.031, respectively). The multivariate analysis revealed that age [hazard ratio (HR)=2.157, P=0.008], stage (HR=2.234, P<0.001), resection margin status (HR=2.748, P=0.004) and TP expression (HR=2.014, P=0.039) were independently associated with overall survival (OS).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2013.166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915652PMC
November 2013

Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with renal insufficiency.

Eur J Cancer 2014 Mar 11;50(4):746-52. Epub 2013 Dec 11.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Research Institute, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Background: Patients with metastatic renal cell carcinoma (mRCC) with renal insufficiency are generally excluded from clinical trials, despite their increasing numbers. Thus, we evaluated the efficacy and toxicity of sunitinib in such patients.

Patients And Methods: Korean patients with mRCC with renal insufficiency who had received sunitinib as first-line treatment between January 2008 and May 2012 were included. Patient characteristics, clinical outcomes and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) were determined according to the degree of renal impairment.

Results: The median age of the 34 patients evaluated was 66 years, 90% had an Eastern Cooperative Oncology Group performance status of 0 or 1 and the median glomerular filtration rate was 46.5 mL min(-1) · 1.73 m(-2) (range, 21.1-59.5). The starting sunitinib dose was 37.5 and 50mg for 12 and 22 patients, respectively. A 4-weeks-on-2-weeks-off regimen was followed for 31 patients; a 2-weeks-on-2-weeks-off regimen, for one patient; and a daily regimen, for two patients. The best response was partial response in eight patients and stable disease in 12. Median OS and PFS times were 26.3 months (95% confidence interval [CI]: 17.1-35.3) and 12.2 months (95% CI: 10.2-13.2), respectively. Common non-haematologic adverse events (AEs) were stomatitis, rash, general oedema and fatigue. The most common AEs of ⩾ grade 3 severity were fatigue, neutropenia and thrombocytopenia.

Conclusions: In patients with mRCC with renal insufficiency, sunitinib was efficacious and did not cause increased toxicity. Thus, clinicians should not hesitate to treat patients with mRCC with renal insufficiency with sunitinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2013.11.029DOI Listing
March 2014

Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy.

BMC Cancer 2013 Jul 22;13:350. Epub 2013 Jul 22.

Department of Internal Medicine, Dong-A University College of Medicine, 3-1 Dongdaeshin-dong, Busan, Seo-gu 602-715, Korea.

Background: Several inflammatory response materials could be used for prediction of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring system in various cancers. The objective of this study was to determine whether the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX).

Methods: The study population consisted of 174 advanced gastric cancer patients. Patients were treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals. The NLR and PLR were calculated from complete blood counts in laboratory test before and after first cycle of chemotherapy.

Results: NLR was a useful prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005), but was not associated with progression free survival (PFS) (p = 0.461). The normalization of NLR after one cycle of chemotherapy was found to be in association with significant improvement in PFS (5.3 months vs. 2.4 months, p < 0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p = 0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR: 2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI: 1.038-2.090, p = 0.030) were independent prognostic markers for OS.

Conclusion: This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent prognostic factor for OS in patients with advanced gastric cancer treated with chemotherapy. These specific factors may also help in identifying the patients, who are more sensitive to FOLFOX regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2407-13-350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729814PMC
July 2013