Mi-Jung Kim

Outcome of endoscopic therapy for cancer bleeding in patients with unresectable gastric cancer.

Gastric cancer bleeding is not rare complication in patients with advanced gastric cancer (AGC). The aim of this study was to evaluate the efficacy and clinical outcomes of endoscopic therapy (ET) for upper gastrointestinal bleeding (UGIB) from unresectable AGC.

Outcomes of second self-expandable metallic stent insertion for malignant gastric outlet obstruction

BackgroundSelf-expandable metallic stents are used widely to relieve malignant gastric outlet obstruction (GOO). However, restenosis or migration of first stents is a frequent complication. The purpose of this retrospective cohort study was to evaluate the effectiveness of second stents as an approach to manage failure of first stents in patients with malignant GOO.MethodsA total of 222 patients with gastric cancer received first stents due to inoperable GOO at National Cancer Center in Korea between January 2008 and June 2011. Monthly follow-up interviews were performed, and second stents (stent-in-stent or stent-after-migration) were inserted in 59 patients by June 2012. Technical and clinical successes and long-term complications were evaluated.ResultsThe technical and immediate clinical success rates were 98.3xa0% (58/59) and 91.5xa0% (54/59), respectively. Patients who received a second stent due to late complications involving the first stent (migration, restenosis, and fracture) showed a higher clinical success rate (95.8xa0% [46/48]) than patients who received a second stent due to immediate clinical failure of the first stent (72.7xa0% [8/11], pxa0=xa00.04). The immediate clinical success rate of stent-after-migration (100xa0% [11/11]) was not different from that of stent-in-stent (89.6xa0% [43/48], pxa0=xa01.0). The stent dysfunction rate of stent-after-migration (27.3xa0% [3/11]) also was similar to that of stent-in-stent (29.2xa0% [14/48], pxa0=xa01.0). The median patencies of stent-in-stent and stent-after-migration were 27.4 and 58.4xa0weeks, respectively (pxa0=xa00.177). There were no significant prognostic factors for patency of second stents.ConclusionsInsertion of a second stent is effective for treating the first-stent failure in gastric cancer patients with GOO, especially if the immediate outcome of the first stent was successful.

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

BackgroundWe conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome.MethodsPatients with LAGC [clinical stage III–IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40xa0mg/m2 twice daily on days 1–14; intravenous docetaxel 35xa0mg/m2 on days 1 and 8, every 3xa0weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.ResultsFrom October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4xa0% (95xa0% CI, 61.4–87.4xa0%), and the R0 resection rate was 97.7xa0%. Clinical downstaging in T or N occurred in 41.9xa0% of patients. The 3-year progression-free survival (PFS) rate was 62.8xa0% and 5-year overall survival (OS) rate was 69.6xa0%. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur Cmax and worse survival than those with wild/wild or wild/variant genotypes.ConclusionPerioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.

FAIRY: a randomized controlled patient-blind phase III study to compare the efficacy and safety of intravenous ferric carboxymaltose (Ferinject®) to placebo in patients with acute isovolemic anemia after gastrectomy - study protocol for a randomized controlled trial

BackgroundIsovolemic anemia (decrease in hemoglobin concentration with normal or even increased blood volume) after gastric cancer surgery may negatively influence short- and long-term outcomes. Therefore correction of isovolemic postoperative anemia is supposed to be beneficial. This prospective randomized placebo-controlled multicenter trial is designed to evaluate the efficacy of ferric carboxymaltose administration with the primary end point of successful hemoglobin level increase by 2xa0g/dl at 12xa0weeks after randomization.Methods and designGastric cancer patients after oncologic resection and postoperative hemoglobin levelu2009≥u20097xa0g/dl to <10xa0g/dl at postoperative days 5 to 7 will be eligible for trial inclusion. After randomization, 450 patients (225 per group) are going to be subjected either to administration of ferric carboxymaltose (treatment group) or normal (0.9%) saline (placebo group). Patients will be blinded to the intervention. Patients will undergo evaluation for hemoglobin level, hematology and quality of life assessment 3 and 12xa0weeks after randomization.DiscussionCorrection of isovolemic postoperative anemia in gastric cancer patients after oncologic resection is considered to be beneficial. Administration of ferric carboxymaltose is considered to be superior to placebo for anemia correction without the possible risks of red blood cell transfusion. Further, improved quality of life for patients with quick recovery of hemoglobin levels is expected.Trial registrationNCT01725789 (international: http://www.clinicaltrials.gov) and NCCCTS-12-644 (NCC, Korea).

Effect of a Proton Pump Inhibitor on Tumor Bleeding Prevention in Unresectable Gastric Cancer Patients: a Double-Blind, Randomized, Placebo-Controlled Trial

Purpose Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. Materials and Methods This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). Results This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Grays test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Grays test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. Conclusions Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

Survival Benefit of Perioperative Chemotherapy in Patients with Locally Advanced Gastric Cancer: a Propensity Score Matched Analysis

Purpose It has been reported that the survival of patients with locally advanced gastric cancer (LAGC) is better in East Asia countries than in developed western countries; however, the prognosis of LAGC remains poor. This study aimed to evaluate the effects of perioperative chemotherapy on the long-term survival of East Asia patients with LAGC. Materials and Methods From October 2006 through August 2008, 43 patients with LAGC received perioperative S-1 combined with weekly docetaxel in a phase II study (neoadjuvant group). These patients were matched using propensity scores to patients who underwent surgery without neoadjuvant chemotherapy during the same period (surgery group). The surgical outcomes and long-term survivals were compared between the 2 groups. Results After matching, 43 and 86 patients were included in the neoadjuvant and surgery groups, respectively, and there was no significant difference in their baseline characteristics. Although the operating time was longer in the neoadjuvant group, there was no significant difference in postoperative complications between the 2 groups. The neoadjuvant group had a significantly higher 5-year overall survival (OS) rate (73.3% vs. 51.1%, P=0.005) and a trend towards higher 5-year progression-free survival (PFS) (62.8% vs. 49.9%, P=0.145). In the multivariate analysis, perioperative chemotherapy was an independent factor for OS, with a hazard ratio of 0.4 (P=0.005) and a marginal effect on the PFS (P=0.054). Conclusions Perioperative chemotherapy was associated with better long-term survival without increasing postoperative complications in the setting of D2 surgery for patients with LAGC, suggesting that perioperative chemotherapy can be a therapeutic option in East Asia countries.

Abstract LB-172: A randomized phase II study of S-1 versus capecitabine as first-line chemotherapy in the elderly metastatic gastric cancer patients with/without poor performance status: clinical and pharmacogenetic results.

Introduction: This study investigated the efficacy and safety of S-1 vs. capecitabine in elderly patients (pts) with metastatic gastric cancer (MGC) with/without poor performance status (PS), and examined the association between CYP2A6 polymorphisms and treatment outcomes. Methods: Eligibility criteria included MGC, measurable lesion(s), no prior chemotherapy for MGC, and age of 70-85 yrs with ECOG PS 0-2 or age ≥ 65 and 2 bid or capecitabine 1250 mg/m 2 bid on days 1-14 every 3 weeks. The primary endpoint was overall response rate (ORR) with time to progression (TTP), overall survival (OS), quality of life (QOL), safety, and the association between CYP2A6 genotypes ( *1 , *4 , *7 , *9 , *10 ) and treatment outcomes as secondary endpoints. Results: From May 2007 to July 2010, 107 pts were randomized to receive either S-1 (n=53) or capecitabine (n=54). Baseline characteristics were well balanced between the two arms (S-1:capecitabine): median age, 72 yrs (range, 64-81):71 yrs (65-78); male, 74%:81%; and PS 0/1, 85%:83%. The median number of cycles was 4 (range, 1-26) in S-1 arm and 5 (1-32) in capecitabine arm. The incidence of G3/4 neutropenia was 3.8% in each arm, and the most common G3/4 non-hematological toxicities included anorexia (21.2% with S-1 vs. 7.5% with capecitabine), fatigue (13.5% vs. 15.1%), and nausea (7.7% vs. 1.9%). S-1 arm had higher incidences of vomiting (40.4% vs. 17.0%; P =0.010) and tearing (51.9% vs. 28.3%; P =0.017), and lower incidence of HFS (25.0% vs. 58.5%; P =0.001) than capecitabine arm. Of the 49 pts assessable for response in each arm, the ORR was 28.6% (95% CI, 15.9-41.3%) in S-1 arm and 26.5% (95% CI, 14.1-38.9%) in capecitabine arm. The median TTP was 3.2 months (95% CI, 1.6-4.8 months) in S-1 arm and 3.4 months (95% CI, 2.5-4.3 months) in capecitabine arm ( P =0.825), and median OS was 8.5 months (95% CI, 6.1-10.9 months) and 10.3 months (95% CI, 7.1-13.5 months), respectively ( P =0.691). CYP2A6 polymorphisms were associated with the efficacy of S-1. Pts having two variant alleles ( V / V ) had inferior efficacy to those having no or one variant allele ( W / W or W / V ): median TTP 2.3 vs. 4.1 months ( P =0.062), and median OS 6.4 vs. 11.5 months ( P =0.034). However, the efficacy of capecitabine did not differ according to CYP2A6 genotypes: median TTP was 3.6 months in V / V pts vs. 3.3 in W / W or W / V ( P =0.257), and median OS was 11.6 vs. 10.2 months ( P =0.756), respectively. In pts with V / V genotype, capecitabine arm had better TTP (median, 3.6 vs. 2.3 months; P =0.062) and OS (median, 11.6 vs. 6.5 months; P =0.090) than S-1 arm. Conclusions: Both S-1 and capecitabine were active and tolerable for elderly MGC pts with/without poor PS with different toxicity profiles. Genotyping for CYP2A6 might provide useful information for treatment selection. Citation Format: Sook Ryun Park, Sun-Young Kong, Mi-Jung Kim, Min Kyeong Kim, Byung-Ho Nam, Mihee Choi, Young-Iee Park. A randomized phase II study of S-1 versus capecitabine as first-line chemotherapy in the elderly metastatic gastric cancer patients with/without poor performance status: clinical and pharmacogenetic results. [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 LB-172. doi:10.1158/1538-7445.AM2013-LB-172

A randomized phase II study of S-1 versus capecitabine as first-line chemotherapy in elderly metastatic gastric cancer patients with or without poor performance status: clinical and pharmacogenetic results

Objective This study investigated the efficacy and safety of S-1 versus capecitabine in elderly patients with metastatic gastric cancer (MGC), and examined the association between cytochrome P450 2A6 (CYP2A6) polymorphisms and treatment outcomes. Materials and methods MGC patients 70–85 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0–2 or 65–70 years old with ECOG PS 2 were randomized to receive S-1 40u2009mg/m2, twice daily, or capecitabine 1250u2009mg/m2, twice daily, on days 1–14 every 3 weeks. Results From May 2007 up to July 2010, 107 patients were enrolled. G3/4 neutropenia developed in 3.8% of each arm, and the most common G3/4 nonhematological toxicities were anorexia and fatigue. Vomiting and tearing were more frequent with S-1 and hand–foot syndrome with capecitabine. The primary endpoint, the overall response rate, was 26.4% (14/53, 95% confidence interval: 14.5–38.3%) in S-1 and 24.1% (13/54, 95% confidence interval: 12.7–35.5%) in capecitabine, both of which exceeded the null hypothesis response rate of 10%. The median time to progression (TTP; 3.2 vs. 3.4 months, P=0.813) and overall survival (OS; 8.5 vs. 10.3 months, P=0.691) were similar in both arms. CYP2A6 polymorphisms were associated with S-1 efficacy. In the S-1 arm only, patients with CYP2A6 variant/variant alleles had worse TTP and OS than those with wild/wild or wild/variant alleles, and in multivariate analysis, the CYP2A6 genotype was predictive for TTP and OS. Conclusion Both S-1 and capecitabine were active and tolerable for elderly MGC patients. The CYP2A6 genotyping might guide treatment selection.

Deep Learning–Based Survival Analysis Identified Associations Between Molecular Subtype and Optimal Adjuvant Treatment of Patients With Gastric Cancer

Purpose Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial. Patients and Methods We developed a novel deep learning–based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data. Results The mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone. Conclusion Our SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.

A randomised phase II study of continuous versus stop-and-go S-1 plus oxaliplatin following disease stabilisation in first-line chemotherapy in patients with metastatic gastric cancer

OBJECTIVESnWe compared continuous versus stop-and-go chemotherapy after disease stabilisation with induction chemotherapy in the first-line treatment of metastatic gastric cancer (MGC).nnnMETHODSnMGC patients who achieved disease control after 6 cycles of S-1/oxaliplatin (SOX) were randomised to receive either continuous SOX until progression (continuous arm) or to have a chemotherapy-free interval followed by SOX reintroduction at progression (stop-and-go arm). The primary end-point was overall survival (OS).nnnRESULTSnOf the 250 patients enrolled, 247 participated in the induction phase. Of these, 121 patients were randomised to the continuous arm (nxa0=xa059) or the stop-and-go arm (nxa0=xa062). Progression-free survival (PFS) was significantly longer in the continuous arm than in the stop-and-go arm (10.5 versus 7.2 months; hazard ratio [HR] 0.55, 95% CI, 0.37-0.81; Pxa0=xa00.002). Duration of disease control (DDC) and OS, however, were comparable between the two arms: median DDC, 10.5 versus 11.3 months, HR 0.92 (95% CI, 0.62-1.36; Pxa0=xa00.674); median OS, 22.6 versus 22.7 months, HR 0.78 (95% CI, 0.50-1.23; Pxa0=xa00.284). Adverse events including grade ≥3 fatigue (28.8% versus 8.1%; Pxa0=xa00.003) and sensory neuropathy (25.4% versus 9.7%; Pxa0=xa00.022) occurred more frequently in the continuous arm than in the stop-and-go arm. Quality of life (QOL) including global health status, physical/role functioningxa0and other symptom scores significantly favoured the stop-and-go arm.nnnCONCLUSIONnCompared with the stop-and-go strategy, maintenance chemotherapy improved PFS but not DDC and OS and had a negative impact on QOL, suggesting the stop-and-go strategy may be an appropriate option in MGC patients following induction chemotherapy.