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Purpose Sarcopenia is a poor prognostic factor in cancer patients, and exercise is one of the treatments to improve sarcopenia. However, there is currently insufficient evidence on whether exercise can improve sarcopenia in patients with advanced cancers. This study examined the feasibility of exercise in advanced gastrointestinal (GI) cancer patients treated with palliative chemotherapy. Methods Between 2020 and 2021, 30 patients were enrolled in a resistance and aerobic exercise program for six weeks. The exercise intervention program (EIP) consisted of low, moderate, and high intensity levels. Patients were asked to select the intensity level according to their ability. The primary endpoint was the feasibility of the EIP measured by compliance during the six weeks. A compliance of over 50% was considered acceptable. The secondary endpoints were changes in weight and muscle mass, safety, quality of life (QoL) and overall survival (OS). Results The median age of the study’s participants was 60 (30–77). The total compliance to the EIP was 63.3% (19/30 patients). Sixteen (53.3%) patients had a compliance of over 80%. The attrition rate was 30.0% (9/30). The mean exercise time was 41.4 minutes, and the aerobic exercise was 92.3% and the resistant exercise was 73.7%, and both exercise was 66.5%. Most patients performed the moderate intensity level exercises at home or near their home. The mean skeletal muscle index (SMI) was 43.5 cm2/m2 pre-chemotherapy and 42.2 cm2/m2 after six weeks of chemotherapy, with a decrease of -1.2 ± 2.8 cm2/m2 (-3.0%) (p = 0.030). In the poor compliance group, the mean SMI decrease was − 2.8 ± 3.0 cm2/m2 which was significantly different (p = 0.033); however, in the good compliance group, the mean SMI decrease was − 0.5 ± 2.5 cm2/m2 which was maintained over the six weeks (p = 0.337). The insomnia was showed a better score (p = 0.042) and there were no serious adverse events. Conclusions The EIP during palliative chemotherapy in advanced GI cancer patients showed good compliance. In the good compliance group, muscle mass and physical functions were maintained for six weeks. The EIP was safe, and the QoL was maintained. Based on this study, further research in exercise intervention in advanced cancer patients is needed.

Background The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. Patients and methods Eighty mPAC patients (age, 19–75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1–2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1–28 every 6 weeks. Results Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p Conclusion Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.

HER2 overexpression or amplification, which is present in 15% of all cases of biliary tract cancer, has been identified as a druggable molecular target by genomic profiling. In the phase 3 ABC-06 trial, the folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen showed a survival benefit compared with active symptom control as second-line therapy for biliary tract cancer. We aimed to evaluate the clinical activity of FOLFOX plus anti-HER2 antibody trastuzumab as a second-line or third-line treatment for HER2-positive biliary tract cancer.This study was an investigator-initiated, open-label, non-randomised, single-arm, multi institutional, phase 2 trial in participants aged 19 years or older with HER2-positive (defined as immunohistochemistry 3+ or immunohistochemistry 2+ and in-situ hybridisation positive or ERBB2 gene copy number ≥6·0 by next-generation sequencing) biliary tract cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) who progressed on chemotherapy containing gemcitabine and cisplatin (with one or two previous chemotherapy lines permitted). In cycle one, patients received intravenous trastuzumab-pkrb at 6 mg/kg on day 1, and FOLFOX (consisting of intravenous oxaliplatin [85 mg/m34 participants were enrolled between June 26, 2020, and Sept 1, 2021. At the time of data cutoff on May 1, 2022, median follow-up was 13·0 months (IQR 11·0-16·9), with three participants remaining on treatment. Ten patients had a partial response and 17 had stable disease; the overall response rate was 29·4% (95% CI 16·7-46·3) and the disease control rate was 79·4% (95% CI 62·9-89·9). Median progression-free survival was 5·1 months (95% CI 3·6-6·7); median overall survival was 10·7 (95%CI 7·9-not reached). The most common treatment-related grade 3 or 4 adverse events were neutropenia (ten [29%] participants with grade 3 and nine [26%] with grade 4), grade 3 anaemia (five [15%] participants), and grade 3 peripheral sensory neuropathy (four [12%] participants). There were no treatment-related cardiac toxic effects or deaths. The overall health assessment (EuroQoL-VAS) score did not change significantly throughout the treatment. Sensory and motor neuropathy symptoms as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy twenty-item scale questionnaire did not change significantly over time.For HER2-positive biliary tract cancer, second-line or third-line trastuzumab biosimilar plus FOLFOX exhibited promising activity with acceptable toxicity, warranting further investigation.Boryung Pharmaceutical, Celltrion, National Research Foundation of Korea, National RD Program for Cancer Control through the National Cancer Center, Yonsei University College of Medicine.

Background This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC). Methods One-hundred-and-sixty-four patients were randomised (1:1) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint. Results In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI: 0.48–0.99), particularly in patients aged p = 0.022). Conclusions The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged

BACKGROUND Clinical impact of the Geriatric Nutritional Risk Index (GNRI) in patients with extensive-stage disease small cell lung cancer (ED-SCLC) have not previously been reported. METHODS This study analyzed 352 patients enrolled in a previous randomized phase III trial comparing the efficacy of irinotecan plus cisplatin with that of etoposide plus cisplatin as the first-line therapy for ED-SCLC. GNRI values were calculated using serum albumin levels and actual and ideal bodyweights. Patients with a GNRI > 98, 92-98, and

Background Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. Patients and methods In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1–14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. Results In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was −12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P Conclusion XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. Trial Registration This study was registered in ClinicalTrials.gov (number NCT01470443).

Purpose: Acute kidney injury (AKI) affects cancer therapy outcome and increases morbidity and mortality in cancer patients. We investigated the incidence, risk factors, and clinical outcomes of AKI caused by palliative chemotherapy in lung cancer patients. Materials and Methods: Between January 2005 and November 2014, 207 lung cancer patients who had been treated with first-line palliative chemotherapy were enrolled. Renal function was assessed during every cycle of chemotherapy. AKI was defined based on changes in serum creatinine levels as described in the Kidney Disease: Improving Global Outcomes guidelines. Clinical outcomes were evaluated depending on AKI occurrence during the first-line chemotherapy. Results: Of the 207 patients, 36 (17.4%) experienced AKI. Among the 36 patients who developed AKI during chemotherapy, 33 (91.8%) had AKI stage I. Although 19 patients (52.7%) with AKI during chemotherapy progressed to chronic kidney disease (CKD), no patients were reported to progress to end-stage renal disease (ESRD). The number of chemotherapy cycles was independently associated with chemotherapy-induced AKI in multivariate analysis (OR = 1.71, 95% CI 1.29-2.26, p < 0.001). The median follow-up duration was 83 months. Patients with AKI during chemotherapy (AKI group) showed significantly longer time to treatment failure than patients without AKI (non-AKI group) (4.2 vs. 2.5 months, p < 0.001). However, the median overall survival (11.7 vs. 8.8 months, p = 0.147) and progression-free survival (5.5 vs. 5.2 months, p = 0.347) were not different between the groups. Conclusions: AKI that developed during chemotherapy was mostly of mild degree and its prognosis was favorable. The occurrence of AKI was associated with the number of chemotherapy cycles administered. AKI did not adversely affect survival of lung cancer patients during chemotherapy.

4096 Background: HER2 over-expression/amplification, which accounts for roughly 15% of total biliary tract cancer (BTC) patients, has been identified as a druggable molecular target by recent genomic profilings, Trastuzumab is a humanized monoclonal antibody against HER2 that has been shown to be effective in patients with HER2-positive breast and gastric cancer, but it has not been studied prospectively in HER2-positive BTC. In the phase III ABC-06 trial, the FOLFOX regimen showed survival benefit as a second-line therapy of BTC. We report the result of a multi-institutional phase II trial of Trastuzumab plus modified-FOLFOX as a second- or third-line treatment for HER2-positive BTC (KCSG-HB19-14; NCT04722133). Methods: HER2-positive (defined as IHC3+ or IHC2+/ISH+ or ERBB2 gene copy number ≥6.0 by NGS) BTC (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of vater cancer) patients who progressed on gemcitabine/cisplatin containing chemotherapy (1 or 2 previous chemotherapy lines permitted) were enrolled. Pts received trastuzumab 4mg/kg (after 6mg/kg load) D1, oxaliplatin 85mg/m2 D1, Leucovorin 200mg/m2 D1, 5-FU 400mg/m2 bolus D1, and 5-FU 2400mg/m2 infusion D1-2 every 2 weeks until unacceptable toxicities or disease progression. The primary endpoint was ORR per RECIST v1.1. Secondary endpoints included PFS, DCR, OS, safety, QOL and correlative biomarker exploration. Results: Total of 34 pts were treated with median follow up of 9.9 months, and 6 pts remained on treatment (treatment duration range: 1.0 to 14.7 months). The primary endpoint was met, with 29.4% (95%CI 15.1-47.5) ORR (PR n = 10), and 79.4% DCR. Median PFS was 5.1 months (95%CI 3.6-6.7) and median OS was not reached (95%CI 7.1-NR; 12-months OS rate 50.6%, 95%CI 29.3-63.6). Pts with HER2 IHC3+ (n = 23, 67.6%) showed tendency for better PFS compared to pts with HER2 IHC 2+/ISH+ (median 5.5 vs 4.9 months, HR 0.52, 95%CI 0.23-1.16). Pts with HER2 3+ tumor cell proportion ≥30% (n = 10) by an artificial intelligence-powered automated HER2 IHC analyzer (Lunit SCOPE HER2) showed significantly better PFS compared to pts without (median 6.67 vs 4.87 months, HR 0.33 95%CI 0.13-0.88). Targeted-panel sequencings were done with tumor tissues from 32 pts and tissue HER2-amplification by NGS did not confer better survival. Treatment-related AE (≥G3) occurred in 29 pts (85.3%) including 19 pts (55.9%) with neutropenia G3-4 and 4 pts (11.8%) with peripheral neuropathy G3-4. No pt showed cardiac AE nor treatment-related study discontinuation. Conclusions: For HER2-positive BTC, 2nd- or 3rd-line trastuzumab plus FOLFOX exhibited a promising efficacy with acceptable toxicity, warranting further investigations. Targeted NGS analyses with ctDNAs from pre-treatment and post-progression liquid biopsies are ongoing. Clinical trial information: NCT04722133.

To identify the vulnerability of recovery sleep, this study investigated the occurrence of obstructive sleep apnea during daytime sleep following overnight flights in healthy airline pilots. We conducted daytime polysomnography following a long-haul night-time flight in 103 pilots. The following variables were assessed: apnea-hypopnea index, respiratory disturbance index and oxygen desaturation index. Moderate-to-severe obstructive sleep apnea was defined as an apnea-hypopnea index ≥15. Seventy-three pilots (70.9%) with no known history of obstructive sleep apnea presented with moderate-to-severe obstructive sleep apnea. Pilots showed high mean apnea-hypopnea, respiratory disturbance and oxygen desaturation indices. The body mass index, Berlin questionnaire score and cumulative flight time contributed to these indices, with both body mass index and cumulative flight time remaining significant at an apnea-hypopnea index ≥15. We found that pilots are vulnerable to obstructive sleep apnea during daytime sleep after night-time flights, which may deteriorate their health, increase fatigue and impair overall flight safety. Further research is needed to ensure flight safety, as daytime recovery sleep is unavoidable for night-time flight pilots. The pilots' normal and recovery sleep patterns should both be studied to develop an effective sleep management protocol.

To determine whether an upfront combination compared to single-agent therapy is beneficial for elderly patients with advanced non-small cell lung cancer (NSCLC) in the real world, a population-based epidemiologic study was conducted.Patients ≥70 years with advanced NSCLC from 2007 to 2012 were identified in the National Health Insurance Service Database of Korea. A Cox proportional-hazards regression model and propensity score analysis were used to examine the effect of treatment modality on survival.Among 41,276 patients newly diagnosed with lung cancer, 8274 (20.0%) identified to be treated with upfront palliative chemotherapy were eligible for this study. After excluding 976 patients who received a first-line anti-epidermal growth factor receptor (EGFR) treatment, 7298 (88.2%) who received cytotoxic chemotherapy were included in further analyses: 5636 (77.2%) received doublet chemotherapy and 1662 (22.8%) received monotherapy. The most frequent regimen in combination group was gemcitabine and platinum doublet (44.7%), whereas that in monotherapy group was gemcitabine (46.7%). Multivariate analyses indicated lower use of combination chemotherapy with increasing age (odds ratio [OR] 0.73; 95% CI 0.67-0.79; P 0.001) and female sex (OR 0.71; 95% CI 0.62-0.80; P 0.001). Receipt of combination over single-agent chemotherapy was associated with a reduced risk of death (hazard ratio [HR] 0.91; 95% CI 0.86-0.96; P = 0.001) in overall population and (HR 0.89; 95% CI 0.80-0.98; P = 0.019) in the propensity-matched cohort.In elderly patients with advanced NSCLC excluding those receiving frontline anti-EGFR targeted agents, receiving initial combination chemotherapy compared to single-agent was associated with improved survival.

Purpose Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. Materials and Methods Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. Results In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). Conclusion Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

BACKGROUND To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p

To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP. This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1–3), moderate (4–6), and severe (7–10) groups. Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0–8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p

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., Epidermal growth factor (EGFR) is an important target for antitumor therapy. This article evaluates the efficacy of EGF ointment for EGFR inhibitor‐related adverse events of the skin.

4119 Background: Modified FOLFIRINOX (mFOLFIRINOX) consisting of 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin has been assessed as second-line treatment of patients with advanced pancreatic cancer in retrospective and phase II studies. However, the result was not confirmed by randomized controlled trial. Methods: A randomized, open-label, phase III trial was conducted at 9 institutions in Korea. Patients with metastatic pancreatic adenocarcinoma (mPAC) and Eastern Cooperative Oncology Group performance status of 0-1 who failed to first-line gemcitabine-based chemotherapy were randomly assigned to receive mFOLFIRINOX or S-1. The primary endpoint was overall survival. Results: A total of 80 patients were enrolled from March 2017 to December 2019. The accrual of patients was early terminated due to clear difference of efficacy in the interim analysis and expectation of poor recruitment due to conflicting adjuvant regimens. Objective response and disease control rates were 15.4% vs. 2.4% ( p= 0.041) and 66.7% vs. 36.6% ( p= 0.007) in the mFOLFIRINOX and S-1 arms, respectively. The median progression-free survival was 5.2 and 2.2 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.002). The median overall survival was 9.2 and 4.9 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.048). The adjusted hazard ratio of the mFOLFIRINOX arm to the S-1 arm for overall survival was 0.402 (95% confidence interval 0.223-0.725, p= 0.002). All grade 3-4 adverse events occurred in 56.5% and 17.1% in the mFOLFIRINOX and S-1 arms, respectively ( p< 0.001). However, only one patient in each arm prematurely discontinued treatment due to toxicity and there was no treatment-related mortality in both arms. Minimally important differences in the health-related quality of life were not observed in both arms. Conclusions: mFOLFIRINOX as second-line treatment in mPAC patients failed to gemcitabine-based chemotherapy demonstrated a survival benefit versus S-1 alone with acceptable toxicities. Clinical trial information: KCT0003534.

TPS4161 Background: Biliary tract cancer (BTC), one of the most fatal cancers with limited treatment options, is generally rare in most high-income countries, but is relatively prevalent in South Korea. Recent genomic profilings have provided druggable molecular targets including HER2 amplification, which accounts for about 15% of total BTC patients. Trastuzumab is a humanized monoclonal antibody against HER2 with known efficacy in patients with HER2-positive breast and gastric cancer, and has not been tested prospectively in patients with HER2-positive BTC. The modified-FOLFOX regimen is currently being tested as a second-line therapy of BTC in phase III ABC-06 trial. This phase II study is investigating the combination of trastuzumab and modified-FOLFOX as second- or third-line treatment in HER2-postivie BTC. Methods: This study (KCSG-HB19-14; NCT04722133) is a phase II, multi-institutional, single arm trial to evaluate the efficacy and safety of trastuzumab plus modified-FOLFOX in gemcitabine/cisplatin refractory patients with HER2-positive BTC. The main inclusion criteria are HER2-positive (defined as IHC3+, or IHC2+/ISH+; ISH+ defined as HER2/CEP17 ≥2.0, or ERBB2 gene copy number ≥ 6.0 by NGS) BTC (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of vater cancer) patients who progressed on gemcitabine/cisplatin containing chemotherapy (one or two previous cytotoxic chemotherapy lines permitted), ECOG 0 or 1, and adequate organ function. Patients receive trastuzumab-pkrb 4mg/kg (after 6mg/kg load) D1, oxaliplatin 85mg/m2 D1, leucovorin 200mg/m2 D1, 5-FU 400mg/m2 bolus D1, and 5-FU 2400mg/m2 infusion D1-2 every 2 weeks until unacceptable toxicities or disease progression. The study has a Simon's two-stage design, with objective response rate (ORR) per RECIST v1.1 as primary endpoint. Secondary endpoints included progression-free survival, disease control rate, overall survival, safety, quality of life and correlative biomarker exploration. Additional patients were to be recruited if pre-specified thresholds for ORR are met at the first stage. The study will enroll up to 34 patients and is currently recruiting at eight sites in South Korea. As of February 2021, 16 patients have been enrolled. The pre-specified activity goal for the first stage of accrual was met; second stage accrual began in February 2021. Clinical trial information: NCT04722133.

9053 Background: While osimertinib showed impressive efficacy and safety profile in 1st-line setting for EGFR mutation-positive (EGFR M+) NSCLC patients, there are no standard targeted therapy following progression. Thus, interest has been growing on sequential treatment of osimertinib as 2nd-line treatment for patients acquiring T790M resistance mutation after 2nd generation EGFR TKIs. We did a retrospective study to support the hypothesis that sequential approach of afatinib followed by osimertinib represents a practical treatment option in ‘real-world’ practice. Methods: In this non-interventional, multicenter study, EGFR M+ NSCLC patients had to start 1st-line afatinib treatment ≥ 13 months prior to data entry. They were categorized into 4 cohorts according to 2nd-line treatments with retesting results: T790M+ patients sequentially treated with osimertinib in cohort A, T790M patients treated with chemotherapy or other treatments in cohort B, and patients with unknown mutation status in cohort C. Cohort D included patients who were still ongoing with afatinib. Primary outcome was the time on treatment (TOT) of patients receiving 1st-line afatinib (TOT-1) followed by 2nd-line treatments (TOT-2). Secondary endpoints were acquisition rate of T790M after progression, objective response rates of afatinib (ORR-1) and 2nd-line treatments (ORR-2), and overall survival (OS). Results: Among a total of 761 enrolled patients, 737 patients excluding 24 screening failures were allocated into cohort A (n=116), B (n=143), C (n=111), and D (n=367). Median age was 62 years (22 - 90) with 53.05% of female proportion. Brain metastasis was discovered in 38.94% at initial diagnosis. Regarding genotypes of EGFR mutations, del19 was 57.53%, 31.48% for L858R, 7.33% for uncommon mutations, and 3.66% for compound mutation. Median TOTs in cohort A, B, C, and D were 35.09 months (95% CI, 30.09 to 43.53), 18.76 months (95% CI, 16.92 to 20.20), 12.02 months (95% CI, 10.22 to 14.98), and 42.61 months (95% CI, 30.95 to 59.23), respectively. Particularly, in cohort A, median TOT-1 and TOT-2 were 17.43 months (95% CI, 15.21 to 19.32) and 11.04 months (95% CI, 7.10 to 14.13), respectively. Retesting was attempted in 262 of 370 patients (70.81%) with 44.27% of T790M detection rate. ORR-1 and -2 in cohort A, B, and C were 84.48% and 56.03%, 82.52% and 29.08%, 54.95% and 21.70%, respectively and 68.94% of ORR for cohort D. Median OS has was not reached. Conclusions: These data suggest that, in real-world practice, sequential afatinib followed by osimertinib be a feasible and effective therapeutic strategy for EGFR M+ NSCLC patients acquiring T790M during the period of afatinib treatment. Of note, median TOT in cohort D is over 3.5 years, suggesting that 1st-line afatinib potentially allow certain patients to maintain long-term, chemotherapy-free state. Further analysis is currently being undertaken and will be presented.

// Hye Ryun Kim 1,* , Joung Soon Jang 2,* , Jong-Mu Sun 3 , Myung-Ju Ahn 3 , Dong-Wan Kim 4 , Inkyung Jung 5 , Ki Hyeong Lee 6 , Joo-Hang Kim 1 , Dae Ho Lee 7 , Sang-We Kim 7 and Byoung Chul Cho 1 1 Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea 2 Department of Internal Medicine, Chung-Ang University, College of Medicine, Seoul, Korea 3 Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea 5 Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Korea 6 Department of Internal Medicine, Chungbuk National University, College of Medicine, Cheongju, Korea 7 Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea * These authors have contributed equally to this study as first authors Correspondence to: Sang-We Kim, email: // Byoung Chul Cho, email: // Keywords : non-small cell lung cancer, epidermal growth factor receptor, nimotuzumab, gefitinib Received : May 24, 2016 Accepted : October 26, 2016 Published : November 03, 2016 Abstract We aimed to evaluate the efficacy of dual inhibition of epidermal growth factor receptor (EGFR) with nimotuzumab (EGFR monoclonal antibody) plus gefitinib (EGFR-tyrosine kinase inhibitor) in advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. An open label, randomized, phase II trial was conducted at 6 centers; 160 patients were randomized (1:1) to either gefitinib alone or nimotuzumab (200 mg, i.v. weekly) plus gefitinib (250 mg p.o. daily) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at 3 months. Of the total 160 enrolled patients, 155 (77: gefitinib, 78: nimotuzumab plus gefitinib) received at least one dose and could be evaluated for efficacy and toxicity. The majority had adenocarcinoma (65.2%) and ECOG performance status of 0 to 1 (83.5%). The median follow-up was 22.1 months, and the PFS rate at 3 months was 48.1% in gefitinib and 37.2% in nimotuzumab plus gefitinib ( P = not significant, NS). The median PFS and OS were 2.8 and 13.2 months in gefitinib and 2.0 and 14.0 months in nimotuzumab plus gefitinib. Combined treatment was not associated with superior PFS to gefitinib alone in patients with EGFR mutation (13.5 vs . 10.2 months in gefitinib alone, P =NS) or those with wild-type EGFR (0.9 vs. 2.0 months in gefitinib alone, P =NS). Combined treatment did not increase EGFR inhibition-related adverse events with manageable toxicities. The dual inhibition of EGFR with nimotuzumab plus gefitinib was not associated with better outcomes than gefitinib alone as a second-line treatment of advanced NSCLC (NCT01498562).

Objectives We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy. Materials and Methods Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined. Results Serum samples from 138 patients (median age: 75 years, range: 70–92 years) were collected from February 2014 to December 2016. During a median follow up time of 13.8 months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, P = 0.009), activin A (P = 0.007), and myostatin (P = 0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32–3.72; P = 0.003) and myostatin (HR 3.02, 95% CI 1.39–6.57; P = 0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model. Conclusion In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation.

Background: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase two trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase two and three trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. Methods: In this open-label, randomized, phase three, non-inferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling 8 cycles. The primary endpoint was to prove the non-inferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. Findings: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5·3 months for the GEMOX group and 5·8 months for the XELOX group. The 6-month PFS rate was 44·5% for the GEMOX group and 46·7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for non-inferiority of XELOX to GEMOX. There was no difference in objective response (p=0·171) and median overall survival (p=0·131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (p

BACKGROUND Although video gaming has been associated with many negative health consequences, it was hypothesized that a mobile online game would help to increase compliance with cytotoxic chemotherapy and decrease the incidence of chemotherapy side effects in patients with breast cancer. OBJECTIVE The potential efficiency of video games to help side effects and improve life quality and life span for metastatic breast cancer patients needs to be demonstrated. METHODS A total of 76 patients with metastatic breast cancer agreed to participate in an education-controlled trial of mobile game healthcare management. All participants were randomly assigned to a chemotherapy+mobile game play group (mobile game group) or a chemotherapy+education group (education group) at a 1:1 ratio. This study was designed as a 3-week prospective trial. RESULTS The mobile game group showed increased drug adherence scores and game playing time compared to the education group. The mobile game group also reported decreased personal total physical side effects (χ2=8.87, p CONCLUSIONS Our findings indicate improved drug compliance, QoL and decreased prevalence rates for physical side effects when using a mobile game for breast cancer patients. These results suggest that the mobile game, ILOVEBREAST, may be helpful in the management of breast cancer. CLINICALTRIAL Clinicaltrials.gov Identifier NCT03205969

Background. A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. Methods. Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was −15%. Results. A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2–5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. Conclusion. RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

In advanced or relapsed pancreatic cancer, mono- or duo-therapy has shown modest efficacy at best. The present study evaluated the efficacy of a triplet combination in relapsed or advanced pancreatic cancer. A total of 37 patients with adenocarcinoma of the pancreas in stage III/IV or with relapsed disease were treated with a gemcitabine, 5-fluorouracil and cisplatin (GFP) regimen every 3 weeks. Only 29 out of 37 patients were evaluable for response due to early treatment interruption in 8 patients. The overall response rate was 24.1% and the disease control rate was 68.9%. The progression-free survival (PFS) rate was 61.5, 30.9 and 17.6% at 3, 6 and 9 months, respectively, and the overall survival (OS) rate was 46.5 and 30.6% at 6 and 12 months, respectively. Grade 3/4 leukopenia, neutropenia and thrombocytopenia occurred in 18.4, 29.9 and 24.5% of 147 cycles, respectively. Old age and a poor performance status (PS) were associated with the early discontinuation of chemotherapy (P=0.038 and P=0.036, respectively). In patients

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. Patients treated with gemcitabine-based palliative treatment were enrolled in this study. Patients were received modified FOLFOX3 (mFOLFOX3) consists of oxaliplatin 85 mg/m2 (day 1) and leucovorin 30 mg (days 1, 2) followed by 5-fluorouracil 1,500 mg/m2 (days 1, 2) every 2 weeks. 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. 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.

Glycoproteins isolated from fruit bodies and mycelial cultures of mushrooms exhibit anti-carcinogenic actions in human cancer cells and animal tumor cells by induction of apoptosis. Here, we report that isoflavone-conjugated glycoproteins (designate Gluvone), exhibit strong anticarcinogenic effects on human breast cancer MCF-7 cells by induction of apoptosis. Gluvone with 9.4 kDa of molecular weight was isolated from submerged-liquid culture of Agaricus blazei mycelia (ABM) in soy flake-containing liquid medium. MCF-7 cells were incubated with various amounts of Gluvone (0~250 μM) for a period of 6 days. Gluvone exhibited anti-proliferative actions in a dose-dependent manner and 62% growth inhibition at 200 μM for 4 days relative to control. Hoechst 33258 staining analysis revealed that Gluvone induced formation of apoptotic bodies. Gluvone was associated with down-regulation of anti-apoptotic Bcl-2 protein expression as well as up-regulation of proapoptotic Bax protein expression. Gluvone treatment induced proteolytic activation of caspase-9 and caspase-3 through cytochrome c release from mitochondria to cytosol as well as concomitant degradation of poly (ADP-ribose) polymerase (PARP). In addition, Gluvone induced activation of caspase-8. Taken all together, these results indicate that the antiproliferative effect of Gluvone is associated with induction of apoptotic cell death through the mitochondrial dysfunction pathway mediated by enhancement of Bax protein expression and suppression of Bcl-2 protein expression.

Background Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. Methods A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods. Results We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. Conclusion Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

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

ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcome of gemcitabine combined with platinum (GP) compared to that of gemcitabine (G) alone in Korean BTC patients. One hundred and fifty-one patients with histologically confirmed biliary tract adenocarcinoma were enrolled at nine institutions between July 2003 and May 2011, including 100 treated with GP and 51 treated with G. With a median follow-up of 7.7 months (range 0.4–38.3 months), the median overall survival (OS) was 12.4 months [95 % confidence interval (CI) 9.4–15.6 months] of the G group, which was not significantly different for the median OS of 11.0 months (95 % CI 9.7–12.3 months) of the GP group (p = 0.599). The median progression-free survival (PFS) was 3.9 months (95 % CI 0.8–7.0 months) in the G group and 3.3 months (95 % CI 2.6–4.0 months) in the GP group (p = 0.504). Overall response rates (ORR) were 18.8 % in G group and 23.9 % in GP group (p = 0.485). There was no significant difference in ORR, PFS, or OS for patients between the G group and the GP group, which was different from the ABC-02 trial. Therefore, gemcitabine monotherapy and GP combination are both effective regimens for Korean BTC patients.

PURPOSE Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens. MATERIALS AND METHODS Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin. RESULTS Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia. CONCLUSION Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS≤2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.

Docetaxel/cisplatin (DP) and gemcitabine/cisplatin (GP) are standard treatment regimens for advanced non-small cell lung cancer (NSCLC). In spite of potent efficacy, the conventional 1-day DP is regarded as having more toxicity as compared with GP. There is increasing interest in a biweekly split administration of DP to reduce its toxicity. Hypothesis was that first-line biweekly DP is as safe as GP in the elderly or poor performance status (PS) patients. Chemotherapy-naive patients with advanced NSCLC (IIIB/IV) who were elderly (65

This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients. This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase. Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated. A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines. ClinicalTrials.gov NCT01636947 ( https://clinicaltrials.Gov/ct2/show/NCT01636947 )

Background Gemcitabine has been recognized as a standard chemotherapy in advanced pancreas cancer (APC). We conducted a phase II study of a triple combination regimen (GPT) consisting of gemcitabine (G), cisplatin (P) and erlotinib (T) in patients with APC. Patients and methods Chemotherapy-naive patients with locally advanced or metastatic, histologically confirmed adenocarcinoma of the pancreas were treated with erlotinib 100 mg daily, 1,000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin administered on days 1 and 8, respectively, every 3 weeks. The primary end point was objective response. Secondary end points included progression-free survival, overall survival and toxicity. The study was designed according to the optimal two-stage design. Results Twenty-two patients were enrolled between June 2009 and August 2010. No complete response was achieved and partial response was observed in 5 patients (26%), Stable disease in 7 (37%), and progressive disease in 7 (37%). The median time to progression was 4.0 months (95% CI: 2.9–5.1 months), and the median overall survival 6.8 months (95% CI: 3.7–9.9 months). The response rate in stage I reached the target (≥3/22, p0 = 10%) established for movement to stage II but this study was determined to close earlier than planned because of unexpected treatment-related deaths (3 patients). Conclusion The triple regimen of GPT is effective for APC. Treatment-related mortalities factored early closure of this GPT protocol. Considering effect and toxicity, this triple regimen seems to offer few benefits to the patients compared with gemcitabine-based doublets. (ClinicalTrials.gov number, NCT00922896).

Summary Background Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. Methods In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m 2 on day 1 and oxaliplatin 100 mg/m 2 on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. Findings 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7–5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6–7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61–1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5–11·5] in the chemotherapy alone group and 9·5 months [7·6–11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69–1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3–4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7–7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1–4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53–1·00; p=0·049). Interpretation Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. Funding None.

PURPOSE The object of this study is to evaluate the efficacy and toxicity of induction chemotherapy followed by concomitant chemoradiotherapy in locoregional esophageal cancer. MATERIALS AND METHODS Between December 1992 and December 1999, 43 patients with locoregional esophageal cancer were enrolled in this phase II trial. Patients were treated with 2-cycles of induction chemotherapy followed by concomitant chemoradiotherapy. F-P chemotherapy consists of 1,000 mg/m2/Day of 5-FU as continuous infusion on day 1~5 and 80 mg/m2 of cisplatin as an intravenous bolus on day 1 and was repeated every 3~4 weeks. All patients received 60 Gy of external beam radiation concomitantly with F-P chemotherapy; intraluminal brachytherapy was added in 12 patients. A total of 4 cycles of chemotherapy were delivered. No further treatment was planned in patients who achieved complete remission after completion of the treatment. RESULTS Among the 43 patients entered, 35 patients completed the protocol. Of the 35 evaluable patients, 12 patients (34%) achieved complete response and 13 patients (37%) achieved partial response. In 26 of 33 patients, dysphagia was improved. At a median follow-up of 22 months, the 2-year and 5-year survival rates were 39% and 19%, respectively. The median survival duration of the complete responder group was 69 months (4~100 months) and the 2-year survival rate of the complete responder group was 82%. Toxicities were tolerable, comprised of mucositis and cytopenia. CONCLUSION Induction chemotherapy followed by concurrent chemoradiotherapy in locoregional esophageal cancer is well tolerated and effective.

The anti-tumor promotional effects of t9,t11-conjugated linoleic acid (t9,t11-CLA) and t10,t12-CLA were evaluated on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication (GJIC) in the human mammary epithelial cell line MCF-10A. The results were compared to those obtained from c9,t11-CLA, which is a more effective anti-tumor promoter on TPA-induced GJIC inhibition in MCF-10A cells than t10,c12-CLA. Cells were treated with 20 μM t9,t11-CLA, t10,t12-CLA, or c9,t11-CLA for 24 h followed by 60 nM TPA for 1 h. Both t9,t11-CLA and t10,t12-CLA equally protected MCF-10A cells from TPA-induced inhibition of GJIC with inferior efficacy to c9,t11-CLA.The protection was due to the ameliorated phosphorylation of connexin43 via suppression of extracellular signal-regulated kinases (ERK1/2) activation. Suppression of TPA-induced reactive oxygen species (ROS) generation by t9,t11-CLA and t10,t12-CLA was less effective, relative to c9,t11-CLA. The results suggest that the anti-promotional activities of t9,t11-CLA and t10,t12-CLA are equal but less potent than c9,t11-CLA in TPA-treated MCF-10A cells. The activity might be mediated by the attenuation of ROS production in MCF-10A cells by preventing the downregulation of GJIC during the cancer promotion stage.

The aim of this study is to evaluate the effect of excision repair cross-complementation group 1 (ERCC1) expression on treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy.One hundred and six patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions in South Korea between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from tissue specimens. Sixty-five patients were treated with cisplatin-based regimens and the other 28 treated with oxaliplatin-based ones.For total study population, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between ERCC1-negative and ERCC1-positive patients, respectively (4.2 vs. 2.9 months, p = 0.116; 7.0 vs. 7.8 months, p = 0.143). In patients treated with cisplatin-based regimens, median PFS and OS were significantly longer in ERCC1-negative group than in ERCC1-positive group, respectively (4.6 vs. 1.9 months, p = 0.014; 9.1 vs. 7.9 months, p = 0.017). Disease control rate (DCR) was better in patients with ERCC1 negative than in patients with ERCC1 positive (p = 0.048). On the other hand, in patients treated with oxaliplatin-containing regimens, median PFS and OS tended to be longer in ERCC1-positive group, but these did not reach statistical significances. Response rate was better in patients with ERCC1 positive (p = 0.005).ERCC1 shows a significant prognostic value in ABTA patients treated with cisplatin. A survival benefit was observed in ERCC1-negative patients from cisplatin-containing chemotherapy but not from oxaliplatin-containing ones. The action mechanism of ERCC1 on cisplatin may be different from that on oxaliplatin.

Sarcopenia is associated with low muscle mass and low physical performance. Here, we performed to evaluate the sarcopenia as prognostic factor and treatment outcomes in older patients with locally advanced rectal cancer (LARC) who received preoperative or postoperative chemoradiotherapy (CRT). LARC patients aged ≥65 years who received either preoperative or postoperative CRT were analyzed retrospectively. Preoperative or postoperative CRT consisted of 50.4 Gy and fluoropyrimidine. Surgery was performed at 6 weeks after CRT completion. Postoperative CRT was performed at 4 weeks after surgery. One month after surgery or CRT, adjuvant chemotherapy was given. Overall survival (OS) and disease free survival (DFS), local recurrence (LR), and prognostic factor were evaluated. Thirty patients received preoperative CRT and 35 patients received postoperative CRT. Five-year OS rate, 5-year DFS rate, or 5-year LR rate was not significantly different between preoperative and postoperative CRT groups (69.0%, 58.5%, and 3.4% vs 73.6%, 67.9%, and 6.9%, P = .56, P = .37, and P = .77, respectively). Age, sex, stage, CEA level, or timing of CRT did not affect OS. However, 5-year OS rate of patients with sarcopenia was significantly lower than those without sarcopenia (38.0% vs 92.5%, P

10045Background: Comorbidities including dyslipidemia, diabetes and coronary heart disease are frequently found in elderly patients with advanced non-small cell lung cancer (NSCLC). Taking statin a...

e22204Background: Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. A combination of serotonin antagonist, olanzapine, and corticost...

10054Background: The efficacy of the EGFR inhibitors has been demonstrated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CRC). Dermatological reactions can ca...

Purpose This trial was conducted to determine the optimal duration of chemotherapy in Korean patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stages IIIB to IV NSCLC who had not progressed after two cycles of chemotherapy were randomly assigned to receive either four (arm A) or two (arm B) more cycles of third-generation, platinum-doublet treatment. Results Of the 452 enrolled patients, 314 were randomly assigned to the groups. One-year survival rates were 59.0% in arm A and 62.4% in arm B, and the difference of 3.4% (95% CI, −8.0 to 4.8) met the predefined criteria for noninferiority. The median time to progression (TTP), however, was 6.2 months (95% CI, 5.7 to 6.7 months) in arm A and 4.6 months (95% CI, 4.4 to 4.8 months) in arm B, the difference of which is statistically significant (P = .001). The frequencies of hematologic and nonhematologic toxicities were similar in the two arms. Conclusion This study confirms the noninferiority of overall survival with four cycles compared with six cycles of chemotherapy for the first-line treatment of advanced NSCLC and supports the current American Society of Clinical Oncology guidelines. Notably, patients receiving six cycles of chemotherapy compared with four cycles showed a favorable TTP, suggesting that further investigation of the new strategies of maintenance therapy with less toxic agents after three to four cycles of induction chemotherapy might be warranted to improve survival, with consideration of both ethnicity and pharmacogenomic signatures.