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In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first-line chemotherapy in advanced gastric cancer.Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm.Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow-up of 12.6 months (range, 0.1-29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.67-1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65-1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand-foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2-1.7).The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first-line treatment of metastatic gastric cancer.

Purpose The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). Materials and Methods Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. Results Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. Conclusion This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

10106 Background: A decision aid (DA) increases knowledge, decreases decisional conflicts and regrets and improves post-decision satisfaction, emotional distress. However, few DA trials have revealed whether decisional role preferences have an impact on patient-reported outcomes by decision making. The objective of this study was to investigate the impact of caregiver’s decisional role preference on decisional conflicts and psychiatric distresses in decision making. Methods: 406 of 444 caregivers of terminally ill cancer patients enrolled onto a previous trial determining the efficacy of the decision aid about disclosure of terminal disease status were included in this analysis. The analysis outcomes were change score of decisional conflicts using the Decision Conflict Scale (DCS) and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) at 1 and 3 months from baseline. Participants were divided into 4 groups: active caregiver who received DA (active-DA), active caregiver in control group (active-control), passive caregiver who received DA (passive-DA), and passive caregiver in control group (passive-control). Linear mixed model was conducted to find out the impact of caregiver’s decisional role preference on the DCS and the HADS. Results: Among 406 caregivers, 137 (33.7%) showed active role preference, and 269 (66.3%) showed passive role preference. In post-hoc analysis of adjusted differences of change scores between passive-DA and active-DA groups, non-significant differences were observed in DCS. However, at 3 months, change scores of HADS depression subscale increased as 4.43 (95% confidence interval (CI), 0.78-8.07; P< 0.007; effect size (ES) 0.71) and those of HADS anxiety subscales increased as 4.14 (95% CI, 0.37-7.91; P= 0.021; ES 0.61) in passive-DA group than in active-DA group, showing moderate to large difference. Conclusions: These findings suggest that information about decision making might be provided with tailored format for how much individual wish to involve in decision making.

Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP). Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen. Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS. In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.

Purpose To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. Materials and Methods A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. Results CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). Conclusion In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.

Purpose Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. Methods Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. Results A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5–39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p

Few studies of systemic chemotherapy have focused on gastric cancer with peritoneal carcinomatosis (PC) without measurable lesions. In the present study, we characterized the outcomes of systemic chemotherapy and prognostic factors for gastric cancer with PC, particularly in patients without measurable disease.Clinical data from 211 gastric cancer patients with PC (137 without and 74 with measurable disease) who had received systemic chemotherapy between January 2003 and December 2010 at a single center were reviewed.The median overall survival (OS) rate of gastric cancer patients with PC with no measurable disease was significantly longer than that of patients with measurable disease (18.0 vs. 11.6 months, p = 0.010). On multivariate analysis, poor performance status [hazard ratio (HR) = 2.15, p 0.001], the presence of metastatic lymphadenopathy (HR = 2.17, p 0.001), and high-grade PC (HR = 1.83, p = 0.001) were associated with significantly decreased OS. When patients with low-grade PC were stratified by clinical PC grade, the median OS of those without measurable disease was 19.6 months. The median OS of patients with low-grade PC with no measurable disease was longer than those of patients with high-grade PC without measurable disease, patients with low-grade PC with measurable disease, and patients with high-grade PC with measurable disease (p = 0.001, p = 0.029, and p 0.001, respectively). Among the patients with low-grade PC, patients who received a gastrectomy had longer survival than patients who did not receive a gastrectomy (p 0.001).In our study, clinically low-grade PC without measurable disease was associated with better outcomes of systemic chemotherapy than the outcomes in the other groups examined. Clinical trials in patients with gastric cancer with PC should be stratified according to PC grade.

Purpose We tested whether a decision aid explaining how to discuss the approach of death with a family member with cancer would help family caregivers decide to discuss a terminal prognosis. Patients and Methods We randomly assigned caregivers of terminally ill patients with cancer to a group that received a video and a companion workbook that showed either how they can discuss the prognosis with their patient (experimental arm) or how cancer pain can be controlled (control arm). At baseline and 1 month, we evaluated the decision to discuss terminal prognosis as the primary outcome. At 0, 1, 3, and 6 months, we assessed the caregivers' decisional conflict and satisfaction as secondary outcomes using a Decision Conflict Scale (DCS). Results We found no difference in changes in the decision to discuss terminal prognosis between the two groups. Conflict (P = .003), uncertainty (P = .019), and value clarity (P = .007) subscale scores and total DCS score (P = .008) improved from baseline to 1 month significantly more in the experimental arm than in the control arm. Over 6 months, the significant between-group differences continued for the conflict (P = .031), uncertainty (P = .014), and value clarity (P = .039) subscale scores and total DCS score (P = .040). Conclusion Decision aids can help caregivers, with the aid of trained professionals, to communicate with patients about their terminal illness.

PURPOSE The potential therapeutic application of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the treatment of multiple myeloma (MM), was recently proposed. However, there have been some problems with the use of TRAIL, due to the appearance of TRAIL-resistant cells in MM. The effect of arsenic trioxide (As2O3) on the rate of apoptosis induced by TRAIL was evaluated in MM cells. MATERIALS AND METHODS Using TRAIL-sensitive (RPMI- 8226) and TRAIL-resistant (ARH-77 and IM-9) MM cell lines, the cell viability, induction of apoptosis, and change in the caspases were examined after treatment with TRAIL alone, or in combination with various concentrations of As2O3. RESULTS Incubating the cell lines with As2O3 augmented the TRAIL-induced apoptosis in the MM cell lines, according to the As2O3 concentration. Apoptosis was mediated through caspase activation. When TRAIL was used alone, caspase8 was activated in the RPMI-8226 cell lines, but not in the ARH-77 and IM-9 cell lines. When As2O3 was added to TRAIL, caspase-9 was activated in the ARH-77 and IM-9 cells. CONCLUSION The use of As2O3, in combination with TRAIL, would help enhance the level of TRAIL-induced apoptosis, and overcome the TRAIL-resistance, in MM cells.

Cyclooxygenase-2 (COX-2) contributes to invasiveness of cancer through activation of several matrix metalloproteinases (MMPs). Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme that degrades the extracellular matrix, and has been linked to invasion and metastasis. This study aims to assess the correlation of the COX-2 expression and the MMP-2 expression in patients with non-small cell lung cancer (NSCLC).We analyzed the protein expressions of COX-2 and MMP-2 by immunohistochemical staining on the tissue array specimens from 204 patients with completely resected NSCLC. A10% immunostaining of the cancer cells was considered negative, while10% was considered positive.The COX-2 expression was positive in 68.1% and that of the MMP-2 was positive in 45.6%. The positive expression rate of MMP-2 (52.5%) in the positive COX-2 group was higher than that in the negative COX-2 group (30.8%, P = 0.004). Furthermore, the MMP-2 expression was associated with lymph node involvement, the tumor stage and the histological type. The patients with a positive MMP-2 expression showed a reduced survival (P = 0.048).The COX-2 expression is associated with the MMP-2 expression in NSCLC patients: the latter may also be associated with tumor progression and reduced survival in NSCLC patients.

Background: This study was undertaken to identify predictors of the prescription of strong opioids, which are important for the management of severe cancer pain, by Korean physicians. Methods: A questionnaire based on a hypothetical case designed to assess the prescription of morphine by physicians was administered to 800 specialists in the Korea Cancer Association, of whom 147 (18.4%) responded, and to 2200 specialists in the Korean Academy of Family Medicine, of whom 388 (17.6%) responded. We used a multidimensional approach to identify the predictors of prescription of morphine by physicians. Results: In the hypothetical case scenario, only 16.5% of the respondents stated that they would prescribe morphine for severe cancer pain. Multiple logistic regression analysis showed that physicians with a positive attitude regarding opioid addiction [odds ratio (OR) 2.62; 95% confidence interval (CI) 1.54 ‐ 4.46], experience of pain assessment (OR 2.09; 95% CI 1.13 ‐ 3.87), recent residency training (OR 2.27; 95% CI 1.30‐ 4.0) and positive self-evaluation as an oncology specialist (OR 2.60; 95% CI 1.41 ‐4.78) were more likely to prescribe morphine. None of the 13 variables in the knowledge dimension significantly predicted prescription of morphine for severe cancer pain. Conclusions: The results of the survey suggest that we need to develop strategies to develop a positive attitude toward opioids, to increase experience in pain assessment and to improve cancer pain

Objectives: We conducted this study to identify factors influencing the burdens cancer brings to a patient’s family and to evaluate the association between the burdens and the caregiver’s quality of life (QOL). Methods: Participants were drawn from the primary family caregivers of cancer patients at 6 university hospitals and the National Cancer Center in Korea. Of the 738 eligible caregivers, 704 (95.4%) completed the questionnaire packets (Family Impact Questions and Caregiver’s QOL-Cancer). Results: Caregivers, who were poor (OR, 2.11; 95% CI, 1.44–3.10), whose health status was poor (OR, 1.87; 95% CI, 1.29–2.70), who were married (OR, 1.75; 95% CI, 1.12–2.72), who provided care for a long time (OR, 2.29; 95% CI, 1.59–3.28), who cared for patients with poor performance status (OR, 1.35; 95% CI, 1.00–1.82), and who paid high medical expenses (OR, 1.70; 95% CI, 1.21–2.40), were more likely to lose their family savings. In multiple regression analysis, most burden variables – including requiring caregiving assistance, major life change, inability to function normally, loss of savings, loss of income, and altered educational plans – were associated with caregiver QOL. Loss of family income, which was related to economic issues, was most strongly associated with it (16.0%). Conclusions: Our study suggests that to improve caregiver QOL, we should give priority to decreasing the economic burden that cancer places on patient’s family.

Background: Intrahepatic cholangiocarcinoma is a chemoresistant cancer for which effective chemotherapy is not yet available. We investigated the efficacy and toxicity of the combination of gemcitabine and cisplatin as second-line chemotherapy in four patients with advanced, progressive intrahepatic cholangiocarcinoma. Methods: Four patients were enrolled who had previous chemotherapy with epirubicin, cisplatin and protracted infusion of 5-FU. All these patients treated with gemcitabine 1000 mg/m 2 intravenously (i.v.) on days 1 and 8 for 30 min, cisplatin 75 mg/m 2 i.v. on day 1 for 90 min, given every 21 days. Results: Two patients had partial response (PR), and two had stable disease (SD), with one of the latter showing a decrease in tumor size of 35%. Median time to progression was 5 months (range, 3-9 months) and median survival was 9 months (range, 8-16 months). Toxicity was mild and tolerable. Conclusions: Gemcitabine and cisplatin combination chemotherapy may be an effective regimen for advanced intrahepatic cholangiocarcinoma. Further study is warranted to determine the efficacy of this combination regimen.

Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma.On day 1, epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered i.v., repeated every 21 days. 5-FU (200 mg/m(2)/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study.Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy.ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.

Purpose To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient. Patients and Methods We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea. Results 380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P < .001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41). Conclusion Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.

Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients. Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated. Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71–89) in the single regimen group (SG, 70 patients) and 73 years (range 71–81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85–5.95) and 4.1 months (95 % CI 2.62–5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17–9.08) and 7.6 months (95 % CI 5.50–9.69; P = 0.782), respectively. Hematologic (P

Background Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. Methods From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. Results The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). Conclusions MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.

Objectives: Terminal cancer patients and their caregivers often experience traumatic stress and need many types of assistance. In the present study we interviewed terminally ill cancer patients and caregivers to determine how much burden they experienced and to find out what factors are most important for satisfaction. Design: We constructed a questionnaire including overall care burden and needs experienced, and administered it to 659 terminal cancer patients and 659 important caregivers at 11 university hospitals and 1 national cancer center in Korea. Results: Finally, 481 terminal cancer patients and 381 caregivers completed the questionnaire. Care burden was not insubstantial in both and the caregiver group felt more burden than the patient group (P

PURPOSE It is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients. MATERIALS AND METHODS We retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death. RESULTS During the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death. CONCLUSION Our results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives.

4016Background: Paclitaxel is currently only available as an IV formulation. DHP107 is a novel oral formulation composed of lipid ingredients and paclitaxel. DHP107 has demonstrated comparable effi...

Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (CDH1, CTNNB1, ERBB2, KRAS, MLH1, PIK3CA, SMARCB1, and TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, CTNNB1, ERBB2, KRAS, and PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.

Objectives: To investigate in depth the use of complementary and alternative medicines (CAMs) by cancer patients at the end-of-life (EOL) and how they communicate with physicians about them. Design and location: In 17 hospitals in Korea between January and December 2004 we identified 4,042 families of cancer patients. Results: The prevalence of CAM use among cancer patients at the EOL was 37.0%, and 93.1% had used pharmacologic types of agents. The most frequent motive for CAM use was the recommendation of friends or a close relative (53.4%) or a physician (1.6%). Only 42.5% discussed CAM use with their physicians. Satisfaction with CAMS was recalled for 37.1% . The most common reason given for that satisfaction was improvement of emotional or physical well-being, while ineffectiveness was the most common reason given for dissatisfaction. The average cost of CAM during the last month of life was $US 900. CAM use was associated with longer disease periods, primary cancers other than liver, biliary, and pancreatic, and need of support from physicians or religion. Conclusions: CAM use among cancer patients at the EOL was common, not discussed with physicians, and associated with expectation of cure. Expectations were generally unmet while the treatments were a financial burden. Further studies evaluating the effects of CAM at the EOL and factors that enhance communication with the physician are needed.

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35 mg/m(2)) intravenously on day 1 and 8 plus oxaliplatin (100 mg/m(2)) intravenously on day 1 every 3 weeks until disease progression or unacceptable toxicity.A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6 months (range, 1-48 months) were enrolled in this trial; 22 (64.7 %) patients had been exposed to both agents. Their median age was 58 years (range, 50-68 years). The overall response rate was 55.9 % (95 % confidence interval (CI), 38.3-73.5 %), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5 months (range, 9.2-50.7 months), the median progression-free survival for all patients was 5.3 months (95 % CI, 4.4-6.1 months) and the median overall survival was 13.8 months (95 % CI, 11.1-16.4 months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1 %) and diarrhea (17.6 %), respectively. Five patients (14.7 %) experienced febrile neutropenia.Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m(2) in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 400 mg/m(2) as a bolus followed by 600 mg/m(2) as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Aim: Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms. Methods: We performed a retrospective analysis of patients who had appendectomies between 1991 and 2007 at five centers in South Korea. Results: Overall 55 patients (19 men, 36 women, median age 61 years) were identified. Of these, 37 (67.3%) were mucinous adenocarcinomas, 14 (25.5%) were intestinal-type adenocarcinomas, and four (7.3%) were signet ring cell carcinomas. The distribution of stages was: 26 (47.3%) with localized disease, five (9.1%) with regional disease, and 24 (43.6%) with distant metastatic disease. The overall 3- and 5-year survival rates among all patients were 72.2% and 64.0%, respectively, with 20 deaths during the follow-up period. In a multivariate analysis, high histological grade (hazard ratio [HR]vs low grade 15.7; P = 0.001) and pathological stage (distant vs loco-regional, HR 6.2; P = 0.021) were independent predictors of overall survival. Of the 34 patients who underwent curative resections of primary appendiceal carcinomas, the 3- and 5-year disease-free survival rates were 66.4% and 53.3%, respectively. The recurrence rate was higher in patients with regional lymph node metastasis (HR vs node negative disease 23.4; P = 0.005) and high-grade tumors (HR vs low grade 6.3; P = 0.029). Additionally, a right hemicolectomy reduced the risk of recurrence (HR vs lesser procedures 0.05; P = 0.005). Conclusion: High tumor grade and advanced stage were significantly predictive of poor survival outcome in patients with primary appendiceal carcinomas.

Painful ophthalmoplegia (PO) and concomitant numb chin syndrome (NCS) is a very rare event. There are a few reports in the literature about PO and concomitant NCS that have preceded the diagnosis of a malignancy. In this report, we describe a patient with diffuse large B cell lymphoma who presented with PO and concomitant NCS as the initial symptom of the disease.

The goal of this study was to investigate the utilization of and attitudes toward life-sustaining treatments (LSTs) at the end of life. We identified 4,042 families of cancer patients who had died at any of 17 hospitals in Korea during 2004. Among those, we analyzed the interviews provided by 1,592 (39.4%) primary caregivers. Only women who provided information in baseline and follow-up point could be included for internal comparison. Most caregivers did not discuss with their patient the option of utilizing the intensive care unit (ICU; 92.7%) or cardiopulmonary resuscitation (CPR; 93.7%) to prolong an ending life. Logistic regressions indicated that the ICU was more likely to be utilized when patients experienced an unexpected medical problem before dying, discussed the ICU with the family caregiver, or were low-educated. CPR was more likely to be used if the patient died within 6 months of diagnosis or the family caregiver was

Family caregivers play an important role in caring for cancer patients, but the impact of caregivers' unmet needs on the quality of end-of-life (EOL) care they deliver and on their workplace performance are less understood.We identified 1,662 family caregivers of cancer patients who had died at any of 17 hospitals in Korea during 2004. The caregivers answered a telephone questionnaire about needs that were not met when they delivered terminal cancer care and how those unmet their needs affected their workplace performance; they also answered the Quality Care Questionnaire-End of Life (QCQ-EOL).Compared with caregivers who did not have unmet needs, caregivers who had unmet needs for symptom management, financial support, or community support showed poorer QCQ-EOL scores (P0.01). Caregivers who had unmet needs for financial support (adjusted odds ratio (aOR) = 7.55; 95% confidential interval (CI) 3.80-15.00), psychosocial support (aOR = 6.24; 95% CI 2.95-13.05), symptom management (aOR = 3.21; 95% CI 2.26-4.54), community support (aOR = 3.82; 95% CI 2.38-6.11), or religious support (aOR = 4.55; 95% CI 1.84-11.26) were more likely to experience work limitations. Caregivers of patients receiving conventional hospital care were more likely to have unmet needs for symptom management (aOR = 1.21; 95% CI 1.00-1.47), psychosocial support (aOR = 1.99; 95% CI 1.37-2.88), and religious support (aOR = 1.73; 95% CI 1.08-2.78) than those of patients receiving palliative hospice care.Caregivers' unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.

Purpose To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT). Methods and Materials We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8–2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1–113.6 months). Results Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT. Conclusion Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

Background: This national survey was undertaken to propose the classification of extranodal natural killer (NK)/T-cell lymphoma (NTCL) subtypes and to clarify a clinical heterogeneity. Patients and methods: Two hundred and eighty patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset. Results: NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset. Conclusion: NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.

Objectives: We investigated the frequency of chemotherapy use and its associated factors in patients in all age groups in the last year of life. Methods: We identified cancer patients who died in 2004 in any of 17 hospitals. We used demographic and treatment characteristics by computerized hospital information systems and by linking the identification numbers to the 2004 death registry. Results: 48.7% of patients in the last 6 months of life, 43.9% in the last 3 months, and 30.9% in the last month of life received chemotherapy. The frequency of chemotherapy use was lower for older patients. In those ≧65 years old, there was no difference between women and men in the proportion that received chemotherapy. For patients Conclusions: Despite the fact that most cancer patients are resistant to chemotherapy at the end of life, it was administered often to all age groups.

Purpose High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. Materials and methods Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m(2) Ara-C and 100 mg/m(2) melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. Results Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1 approximately 62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome>grade 3. Conclusion The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.

TPS4138 Background: Paclitaxel is an antineoplastic agent widely used for treating cancer patients. However, only IV paclitaxel is available on the market. DHP107, a novel oral formulation, is comp...

Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/- 6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001]; mean +/- SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.

Background Survivin, an inhibitor of apoptosis is expressed in several human cancers. Its expression is known to be associated with poor clinical outcome, but not widely studied in pancreatic cancer. We performed this study to determine the survivin expression in pancreatic cancer and its clinical significance as a prognostic factor. Methods We performed immunohistochemical staining for survivin, p53, and Bax in formalin-fixed, paraffin-embedded block from forty-nine pancreatic tissues. To determine the association with clinical course, we reviewed the patients' clinical record. Results Of the 49 cases of pancreatic cancer, 46 cases (93.9%) were positive for survivin expression. There was no significant association between survivin expression and p53 or bax. For clinicopathological parameters, perineural invasion was more common in survivin positive and venous invasion was more common in survivin negative (p = 0.041 and 0.040, respectively). Responsiveness to chemotherapy appeared to be slightly better in patients with low survivin expression. Conclusion Survivin expression may be associated with venous or perineural invasion, indicating metastatic route, and seems to have a potential as a predictive marker for chemotherapy. Further study of large scale is required to determine the clinical significance of survivin expression in pancreatic cancer.

The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer (MBC). We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospective assessment of the predictive values of circulating HER2 extracellular domain (ECD) and vascular endothelial growth factor (VEGF). Docetaxel 75 mg/m 2 and epirubicin 75 mg/m 2 were given intravenously every 3 weeks. Prophylactic G-CSF was not used. Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay. Forty MBC patients were enrolled, and 39 patients were evaluable for toxicities and 38 for response. Complete response was observed in 3 (7.9%) patients, partial response in 20 (52.6%) (overall response rate 60.5%), stable disease in 11 (28.9%) and disease progression in 4 (10.5%). After a median follow-up of 22.5 months, the median duration of response was 28 weeks, median time to disease progression was 32 weeks, and median survival was 15.8 months. Two-hundred and fifteen cycles of treatment were administered (median, 6 cycles per patient). Grade 3 and 4 neutropenia were observed during 24 (11.2%) and 74 (35%) cycles respectively, and grade 3 or 4 febrile neutropenia in 24 (11.2%) cycles. Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration (p

Due to its greater convenience, a combination of uracil and tegafur (referred to as UFT) taken orally is an attractive alternative to continuous intravenous (i.v.) 5-fluorouracil (5-FU) infusion. This phase II study assessed the response rate and toxicity profile of the combination of epirubicin, cisplatin and UFT in patients with metastatic adenocarcinoma of the stomach.Epirubicin (50 mg/m(2)) and cisplatin (60 mg/m(2)) were administered i.v. to 35 patients with metastatic gastric carcinoma on day 1, and subsequently UFT (300 mg/m(2)/day) was administered orally in divided doses for 21 days. The treatment was repeated every 3 weeks. The response rate, time to disease progression, survival and toxic effects were analyzed.Thirty-two of the 35 enrolled patients were assessed subsequently for response. The median number of cycles was four. Thirteen patients (40.6%) showed partial responses, while none showed a complete response. The median time to progression of carcinoma was 20.4 weeks, and the median survival was 37 weeks. Grade 3 and 4 neutropenia was observed in 25% of patients. Grade 3 nausea and vomiting was observed in 28% of patients. No treatment-related death was observed. All patients received doses as planned, except for one who required a 75% dose reduction due to nephrotoxicity. Six of 132 cycles were delayed7 days after four cycles.The combination of epirubicin, cisplatin and UFT showed anticancer activity against metastatic gastric adenocarcinoma, had a tolerable toxicity profile and showed excellent patient compliance.

This study examined cancer patient and family member preferences-and the reasons for the preferences-regarding place of terminal care and of death.We constructed a questionnaire that included demographic, clinical, and support network data for 371 patients who were treated at any of the seven university hospitals or the National Cancer Center in Korea and 281 of their family members.About half of the interviewed patients and half of the family members expressed a preference for the patient being cared for and dying at home. The preference reflected a wish for patients to live out their lives in privacy and to be with their family when their life ended. Those who expressed a preference to be cared for or to die in a hospital wanted to get medical treatment during the last days of life and to relieve their families of the burden of caring for them. Of the variables examined, support network factors and some sociodemographic factors (sex, family members' age, and place of residence) were strongly predictive of preferences.A majority of cancer patients preferred to receive terminal care at home. Cancer patients and family members with strong support groups were more likely to prefer the home as the place of terminal care and dying. Hence, improving support networks might increase the proportion of patients receiving home care and dying at home.

Aim: Capecitabine and cisplatin (XP) combination chemotherapy is one of the standard 1st line regimens for the treatment of metastatic gastric cancer (MGC). Sorafenib is a multi-kinase inhibitor with activity against angiogenesis and RAF-MEK-ERK pathway. In this study, we aimed to evaluate the efficacy of sorafenib (S) in combination with XP as the 1st line chemotherapy in MGC. Methods: This study was a randomized (1:1), open-label, phase II study. The patients (pts) with metastatic gastric or gastroesophageal junction adenocarcinoma with measurable lesion(s) were eligible. The primary endpoint was progression-free survival (PFS). XP + S consisted of capecitaine 800 mg/m2 po bid on days 1-14, cisplatin 60 mg/m2 iv on day 1, and sorafenib 400 mg po bid on days 1-21, every 3 weeks. XP consisted of capecitabine 1000 mg/m2 on days 1-14, and cisplatin 80 mg/m2 iv on day 1, every 3 weeks. XP was continued up to 8 cycles until disease progression or intolerance. Pts in XP arm were allowed to cross over to sorafenib alone when their diseases progressed. Results: Between Jan 2011 and Feb 2013, a total of 195 pts were randomized from 12 sites in Korea, China and Taiwan. Median age was 56 years. All pts had ECOG performance status 0-1. 19% of pts had prior gastrectomy. Overall response rate was 54% in XP + S arm, and 52% in XP arm (p = 0.826). With a median follow-up of 12.6 months (range, 0.1-29.2), median PFS assessed by independent review was 5.6 months in XP + S arm, and 5.3 months in XP arm (HR 0.92, 95% CI 0.67-1.27, p = 0.609). OS was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65-1.31, p = 0.661). Frequencies of grade 3/4 toxicities were similar between XP + S and XP arms, except neutropenia (21% vs 37%), febrile neutropenia (2% vs 6%), and palmar-plantar erythrodysesthesia syndrome (7% vs 1%). In 51 pts who crossed over to sorafenib alone in XP arm, there was no objective response and the median PFS was 1.3 months (95% CI, 1.2-1.7). Conclusions: The addition of sorafenib to XP chemotherapy was safe but not more effective than XP chemotherapy alone for the 1st line treatment of MGC. Biomarker analyses are now ongoing to identify potential patients who can get benefit with XP + S. Disclosure: Y. Kang: Honorarium, consultant for Bayer, Roche Research grant from Bayer, Roche. All other authors have declared no conflicts of interest.

Because dose intensity may be important as a determinant response to vinorelbine, we explored the possibility of increasing the dose intensity of vinorelbine on a daily x4 schedule.Between February 1998 and March 1999, 31 patients with previously untreated advanced non-small cell lung cancer were enrolled. Vinorelbine 15 mg/m2 and cisplatin 20 mg/ m2 were administered intravenously daily for 4 days and repeated every 21 days.A total 96 cycles were administered (median 3, range 1-6); 42% of vinorelbine and 39% of cisplatin injections were dose-reduced or delayed owing to toxicity. The actual dose intensity (DI) of vinorelbine was 17.7 mg/m2/week and that of cisplatin was 24 mg/m2/week. These figures represent 88 and 90% of the theoretical DI, respectively. The overall response rate was 40% (12/30, one CR). The main toxicity was myelosuppression: granulocytopenia WHO grade 3 and 4 in 24 patients (77%) and thrombocytopenia grade 3 in two patients (6%). The non-hematological toxicity was mild and tolerable. After a median follow-up of 7.5 months (range 3-21 months), the median progression-free survival and overall survival times were 5 months (95% CI, 3.8-6.2) and 8 months (95% CI, 4.5-11.5), respectively.This regimen has a comparable therapeutic activity in patients with advanced lung cancers. However, despite supportive care there were excessive hematological toxicities. In view of increased toxicity and similar efficacy, this regimen is not indicated outside a clinical trial.

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.

Mucosa-associated lymphoid tissue (MALT) lymphoma is frequently reported in the gastrointestinal tract (GIT), but the incidence is low in the upper aerodigestive tract. In particular, MALT lymphoma of the tongue is very rare. Only four cases have been reported in the English literature to date. We report a case of 29-year-old woman who had a past history of peripheral T cell lymphoma of the head and neck and a new mass at the right base of tongue 3 years later. An incisional biopsy of the base of tongue revealed a new pathology, one that of extranodal marginal zone B cell lymphoma (MALT lymphoma). After staging work-up, she was diagnosed to be at the Ann Arbor stage IE. She was treated with 30.6 Gy of radiation therapy alone and there was no recurrence after 3 years follow-up.

e15164 Background: Unresectable locally advanced adenocarcinoma (AGC) of the stomach is associated with poor prognosis due to the lack of effective treatment. Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally AGC in the current multidisciplinary treatment model. Paclitaxel and capecitabine (PX) has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. This phase II study was performed to evaluate the efficacy and safety of neoadjuvant PX chemotherapy in patients with unresectable locally AGC. Methods: Patients with AGC, clinically unresectable because of local invasion and/ or conglomerated regional lymph nodes (station 7, 8, and 9) metastasis on based on laparoscopic staging, were enrolled. PX consisted of paclitaxel 175 mg/m2 i.v. on day 1, and capecitabine 835 mg/m2 twice daily p.o. on days 1–14 every 21 days. After three cycles of NAC, patients with clinically resectable AGC underwent surgical resection. Results: This trial was stopped for poor accrual after 18 patients were enrolled; 50% patients had tumors located in the proximal third of the stomach. Seventeen patients finished three cycles of chemotherapy. The overall response rate was 41.2% (7/17 cases), of which 71.4% (10/14 cases) metabolic response. Fourteen (77.8%) of the 18 patients enrolled underwent surgery, and 12 (85.7%) had an R0 resection. Pathological complete response was observed in one (7.1%) of patients. Toxicity was mild to moderate and there were no treatment-related deaths and no major surgical complications. With a median follow-up of 28.6 months (range 6.4-38.4 months), the 2-year survival rate for all patients was 71.1%. Subgroup analysis found R0 resection (35.7 months vs. 20.6 months, P= 0.005) and patients with pathologic N downstaging (P < 0.001) to have improved overall survival. Conclusions: Neoadjuvant chemotherapy with PX shows promising results in unresectable locally AGC patients without increased morbidity and mortality. Neoadjuvant PX may permit a larger chance of curative resection in unresectable locally AGC patients.

Background Pantoparzole(PPZ) is a proton pump inhibitor which is known to have an apoptotic activity in gastric cancer cells. Meanshile, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells. However, some types of cancer cells, including AGS human gastric adenocarcinoma cells show resistance for the TRAIL-mediated apoptosis. This study was aimed to investigate the sensitizing effectcs of PPZ on TRAIL-mediated apoptosis in AGS cell line. Methods Sensitivity to TRAIL and activation of TRAIL-induced apoptotic pathways were analyzed in AGS cell lines. WST-1 method was used to evaluate cell viability; Western blots was used to evaluate TRAIL-induced apoptosis. Results TRAIL alone had little effect on apoptosis in AGS cells. However, treatment with TRAIL in combination with subtoxic concentrations of PPZ sensitized TRAIL-mediated apoptosis in AGS cells. Combined treatment of PPZ and TRAIL induced caspase(caspase-8, -9, -3) and the pro-apoptotic molecules (Bax). In addition, the down regulation of phosphorylated ERK were also found in cells treated with the combination of PPZ and TRAIL. Conclusion The combination of TRAIL and PPZ may be considered as an approach to overcome the resistance of TRAIL in cancer treatment. Citation Format: Sang Young Roh, Jae Ho Byun, Byoungyong Shim, Young Seon Hong. Combination treatment of pantoprazole and TRAIL reduce cell viability by activating caspase cascade and down-regulation of phosphorylated ERK in AGS cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 977. doi:10.1158/1538-7445.AM2013-977

Polycomb repressor complex-2 (PRC-2) is aberrantly expressed in a variety of human malignancies including lung and esophageal cancers. PRC-2 contains three main core proteins, enhancer of zeste 2 (EZH2), suppressor of zeste 12 (SUZ12), and embryonic ectoderm development (EED). In the present study, we sought to examine the effects of PRC-2 expression in lung and esophageal cancers, and to determine if PRC-2 is a potential therapeutic target in these malignancies. qRT-PCR analysis demonstrated significant over-expression of EZH2, SUZ12, and EED in cultured lung and esophageal cancer cells as well as primary tumors relative to normal or immortalized aerodigestive tract epithelial cells, or normal lung or esophageal tissues. Over-expression of individual PRC-2 components appeared to coincide with tumor histology; for example EZH2 was particularly over-expressed in small cell lung cancers, whereas EED appeared to be over-expressed primarily in esophageal cancers. DZNep mediated dose-dependent depletion of EZH2, EED and SUZ12, with corresponding decreases in global H3K27Me3 levels in cultured lung and esophageal cancer cells. Depletion of PRC-2 expression/activity coincided with growth arrest in these cancer cells. The growth inhibitory effects of DZNep in lung cancer cells were recapitulated byshRNA-mediated knock-down of EZH2 in these cells. DZNep induced expression of Dkk-1, a putative tumor suppressor that we have previously reported to be repressed by polycomb-mediated mechanisms in lung cancer cells and cultured normal respiratory epithelia following exposure to cigarette smoke condensate (CSC). Chromatin immunoprecipitation (ChIP) experiments demonstrated that DZNep-mediated activation of Dkk-1 coincided with decreased levels of H3K27Me3 within the Dkk-1 promoter. qRT-PCR and immunoblot experiments revealed that exposure of lung cancer cells to DZNep before or concurrent with CSC abrogated tobacco-mediated repression of Dkk-1 in vitro. Subsequent experiments demonstrated that daily intra-peritoneal (IP) injections of CSC significantly decreased Dkk-1 gene expression in subcutaneous A549 and Calu-6 xenografts, and enhanced growth of these tumors in nude mice. IP administration of DZNep (2.5 mg/kg BID q4 days every 7 days) significantly abrogated the enhancement effect of cigarette smoke on growth of lung cancer xenografts; this phenomenon coincided with decreased EZH2 and increased Dkk-1 expression in these xenografts. Collectively, these findings support development of DZNep for inhibiting PRC-2 expression in thoracic malignancies. Citation Format: Mahadev Rao, Young Hong, Scott Atay, Trevor Upham, Julie Hong, Nicole Datrice, Mary Zhang, Enrique Zudaire, Victor Marquez, David Schrump. Targeting H3K27 Methylation by 3-Deazaneplanocin A (DZNep) in lung and esophageal cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5360. doi:10.1158/1538-7445.AM2013-5360

122 Background: In gastric cancer, platinum and fluorouracil combination chemotherapy (CTx) is commonly used. But the optimal duration of CTx in palliative setting is not known. Thus, we reviewed the pts who rested CTx despite of persistent disease control. Methods: From Mar 2007 to Feb 2012 at Seoul St. Mary’s hospital, we retrospectively reviewed pts as follows; (1) had metastatic or recurrent gastric cancer, (2) received 9 cycles of FOLFOX as 1st-line, (3) had no progressive disease (PD) and rested after completion of 9th cycle. Results: Total 25 pts were reviewed. Median age was 54 (36~77) and 15 pts (60%) were male. 13 pts (52%) had recurrent disease and 12 metastatic initially. All pts were treated with oxaliplatin 100 mg/m2, leucovorin 400 mg/m2 on day 1 and 5-FU 1200 mg/m2 on day 1-2 every 2 weeks. All pts had metastasis; carcinomatosis peritonei (CP, 56%), lymph node (36%), liver (20%) and bone (8%). Nine pts (48%) had non-measurable lesions and 3 no evidence of disease (NED) on CT after palliative surgery. Response evaluation was done every 3 cycles. Among 22 pts with evaluable disease, 5 (20%) showed complete response (CR), 8 (32%) partial response (PR), 2 (8%) stable disease (SD) and 7 (28%) non-CR/non-PD as best response. Median progression free survival (PFS) was 14.2 m (95% CI, 6.6-21.9). The PFS in CP vs. non-CP was 9.9 vs. 21.5 m (log rank P = .037). And PFS according to best response were as follows; 25.5 m in CR + NED group, 15.7 PR, 13.4 non-CR/non-PD and 4.3 SD (log rank P = .014). Other factors did not seem to affect PFS. Conclusions: This study suggested that resting CTx in selected pts would be reasonable in gastric cancer. Especially the presence of CP and the grade of response seemed to be important in patient selection.

Background Platinum agents and oral fluoropyrimidines are widely used in the treatment of advanced gastric cancer. This study was aimed to evaluate the efficacy and safety of two combination regimens (capecitabine plus cisplatin [XP] vs S-1 plus cisplatin [SP]) in patients with untreated recurrent or metastatic gastric cancer. Methods Patients diagnosed as untreated recurrent or metastatic gastric cancer were randomly assigned to either capecitabine (2500 mg/BSA/day; day 1-14) plus cisplatin (60 mg/BSA/day; day 1), every 3 weeks or TS-1 (80-120 mg/day; day 1-14) plus cisplatin (60 mg/BSA/day; day 1), every 3 weeks. Primary end point was overall response rate (ORR), accessed by RECIST criteria (ver. 1.0). The secondary end point was progression free survival (PFS), overall survival (OS), and toxicities. Results 86 patients were anticipated to be enrolled, but 51 patients were randomized to XP (25 patients) arm or SP (26 patients) arm because enrollment was slower than expected. ORR of XP and SP was 52% (13 of 25 assessable patients) vs. 44% (15 of 25 assessable patients), and no significant differences were found (P = 0.778). OS of XP vs. SP was 10.3 months (95% CI; 4.8-15.8) vs. 12 months (95% CI; 9.5-14.5), with no differences (P = 0.785). PFS was 4.6 months (95% CI; 4.6-5.2), 4.4 months (95% CI; 2.2-6.6) each (P = 0.68). The incidence of grade 3-4 neutropenia of XP vs. SP was 40% vs. 43.2%. There were no febrile neutropenia in XP arm, but 7.7% in SP arm. Grade 3-4 thrombocytopenia was 12%, 3.8% each. Other grade 3-4 toxicities were; Nausea (4% vs. 0%), Stomatitis (12% vs. 3.8%), Hand-foot syndrome (16% vs. 0%), Diarrhea (0% vs. 3.8%). Median relative dose intensity of capecitabine vs. TS-1 was 78.7% (range 51.9-116.7%), 87.5% (range 57.1-166.7%). Conclusion There were no significant differences in ORR, OS, and PFS between XP vs. SP arm. The incidence of grade 3-4 neutropenia was similar in both arms, but thrombocytopenia was relatively more common in XP arm. SP was more tolerable than XP in non-hematologic toxicities. Considering the usual dosage of capecitabine in monotherapy is 2500 mg/BSA/day, capecitabine 2500 mg/BSA/day combined with cisplatin 60 mg/BSA may be overdosed, and higher rate of non-hematologic toxicity can be explained. Dosage of capecitabine when combined with cisplatin, needs to be further adjusted for routine use. Disclosure All authors have declared no conflicts of interest.

Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. Disclosure All authors have declared no conflicts of interest.