bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter, phase II study of trastuzumab plus capecitabine and oxaliplatin (XELOX) as first-line chemotherapy for HER2-positive advanced gastric cancer: Update results of efficacy and toxicity.
Authors: Gong Jifang , Liu Tianshu , Fan Qingxia , Bai Li , Bi Feng , Qin Shukui , Wang Jinwan , Xu Nong , Cheng Ying , Bai Yuxian , Liu Wei , Wang Liwei , Shen Lin 
Published: February 2017

102 Background: The ToGA study showed trastuzumab plus chemotherapy prolonged OS in patients with HER2-positive AGC. Result of REAL2 study suggested that oxaliplatin may be as effective as cisplatin but more tolerable. To further improve treatment options, we initiated a study to evaluate the efficacy and safety of trastuzumab plus XELOX in Chinese patients with HER2-positive AGC. Methods: Simon two-stage design with primary endpoint of best confirmed response rate by RECIST 1.0 was applied. The sample size is calculated to be 46, assuming H0=40%, H1=60%, a=0.05, b =0.2. Considering 10% drop-out rate, the total number of subjects was planned to be 51. Patients with previously untreated, HER2-positive (IHC2+/Dual SISH positive, or IHC 3+), histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130mg/m2 infusion, q3w, up to 6 cycles. Capecitabine was given orally with 2000mg/m2d, d1-14, q3w. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The NCI-CTCAE version 4.0 is used to evaluate safety profiles. Results: 72 patients (362 patients at 13 centers were screened) were HER2 positive, of which 51 patients were enrolled. The majority of patients were HER2 IHC 3+ (38/51). Response was evaluated in 46 patients, one patient achieved CR and thirty-three patients achieved PR. Till June 2013, 29 patients progressed, 14 cases died, showing PFS of 312 days (95%CI:211-360). The most common AEs that are higher than grade 3 were thrombocytopenia (21.6%), neutropenia (13.7%), anemia (7.84%), leucopenia (3.92%), nausea/vomiting (3.92%), hand-foot syndrome (3.92%). 6 patients possess LVEF decrease by ≥10% and one patient discontinued trastuzumab infusion. Conclusions: The addition of trastuzumab to XELOX was well tolerated and the results demonstrated encouraging efficacy. Survival benefit of this regimen needs further follow-up of patients to be concluded. Clinical trial information: NCT01364493.
A comparison of carboplatin with paclitaxel and cisplatinum with 5-fluorouracil in definitive chemoradiotherapy in esophageal cancer patients.
Authors: Honing Judith , Smit Justin , Muijs Christina , Burgerhof Johannes , Beukema Jannet , Plukker John Theodorus , Hospers Geke 
Published: February 2017

104 Background: In esophageal cancer (EC) patients not eligible for surgery definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard regime. Nowadays carboplatin and paclitaxel are also often used. In this study we compared survival and toxicity rates between both regimens. Methods: This multicentre study included 102 patients treated in five centres in the North Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU and 55 patients carboplatin/paclitaxel. Results: Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group (P=0.879, Hazard Ratio [HR] 0.97 confidence interval [CI] 0.62-1.51), with a median survival of respectively 16.1 (CI 11.8-20.5) and 13.8 (CI 10.8-16.9) months. Median disease free survival (DFS) was comparable (P=0.760, HR 0.93 CI 0.60-1.45) between the cisplatinum / 5-FU group (11.1 months, CI 6.9-15.3) and the carboplatin/paclitaxel group (9.7 months, CI 5.1-14.4). Groups were comparable except clinical T-stage was higher in the carboplatin/paclitaxel group (P=0.008), but a high clinical T-stage (cT4) was not related to OS and DFS in a univariate analysis (P=0.250 and P=0.201). A higher percentage of patients completed the carboplatin / paclitaxel regimen (82% compared to 57%, P=0.01). Hematological and non-hematological toxicity (≥ grade 3) was significantly lower in the carboplatin / paclitaxel group (4% and 18%) than in the cisplatinum/5-FU (19% and 38%, P=0.001). Conclusions: In this study we show comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared to cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with a higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment for cisplatinum/5-FU is a good candidate regimen for further evaluation.
A province-wide retrospective comparison of pathologic response and progression-free survival in locally advanced esophagus cancer patients treated with either cisplatin-5FU (CF) or carboplatin-paclitaxel (CP) concurrent with radiation (XRT) with or without surgery.
Authors: Schellenberg Devin , Peixoto Renata , Lee Andrea , Lim Howard John 
Published: February 2017

107 Background: The 2012 CROSS trial demonstrated an overall survival (OS) benefit for neoadjuvant, concurrent Carboplatin-Paclitaxel (CP) and radiation versus surgery alone. Based on this trial, the standard chemotherapy treatment for locally advanced esophageal (LAE) cancer in British Columbia (BC) became CP instead of Cisplatin-5FU (CF). This study evaluates the pCR rates and progression free survival (PFS) of those patients treated immediately prior and immediately after the change in provincial standard. Methods: All BC patients with LAE cancer diagnosed between February 2010 and February 2013 who completed at least 40 Gy of neoadjuvant radiation were analyzed. Standard demographics, chemotherapy delivered, radiation dose, surgical pathology and follow-up data were collected. Pathologic response was compared by chi-squared analysis. Patients were followed until death or last follow-up. Survival was compared by log-rank test. Results: Seventy-three patients received CF and 39 received CP. The tumor characteristics of the subgroups were similar: squamous histology was 57% (CF) vs. 49% (CP), node positivity rate on pre-treatment PET scan was 66 vs. 67%, and median tumor length was 5.7 vs. 5.8 cm. Median radiation dose was 50 Gy in both arms. The CP arm was slightly older (Median 66 vs. 61 yo) and had a greater percentage of males (80% vs. 57%). Forty eight and 49% percent of patients were able to undergo resection. The pCR rates were 49% (CF) vs. 16% (CP) (p<0.01) in the surgical subgroups. Median FU was 14.5 (CF) vs. 9.3 (CP) months. Median PFS for all patients was 16.5 (CF) and 14.6 (CP) (p=0.44). Median PFS in surgical patients was 23.4 months (CF) and 14.6 months (CP) (p=0.16. Conclusions: In patients with similar tumor characteristics, XRT with CF resulted in greater pCR rates than with CP. The pCR rate in the CP subgroup is lower than the 29% seen in the trial. With relatively short follow-up, no difference in PFS has yet been identified. [Table: see text]
Updated results of a randomized phase II trial for neoadjuvant versus adjuvant docetaxel/cisplatin chemotherapy in patients with locally advanced gastric cancer.
Authors: Kim Young Woo , Ryu Keun Won , Choi Il Ju , Kook Myeong-Cherl , Park Young Iee , Kim Hark K. 
Published: February 2017

111 Background: Recent phase III trials proved the role of adjuvant chemotherapy in patients with gastric cancer after D2 resection, but the optimal treatment sequence remains to be determined. Here we report long-term follow up results for the randomized phase II trial comparing between neoadjuvant and adjuvant docetaxel/cisplatin (DC) chemotherapy in patients with locally advanced gastric cancer (LAGC). Methods: Patients with LAGC (stage IIIA-IV) were stratified by Japanese staging system and randomized to either neoadjuvant or adjuvant weekly DC chemotherapy in the National Cancer Center of Korea from 2003 to 2005. FDG-PET/CT screening was employed to exclude patients with metastasis. Patients randomized to neoadjuvant arm received 3 cycles of DC regimen (docetaxel 36 mg/m2 and cisplatin 40 mg/m2 on days 1 and 8 every 3 weeks), followed by surgery (D2 dissection). In adjuvant arm, patients underwent surgery, followed by 3 cycles of the same DC chemotherapy regimen. Results: Neoadjuvant arm (n=43) demonstrated higher R0 resection rate than adjuvant arm (n=44) [81% v 73%], but the difference was not statistically significant. At a median follow-up for suriving patients of 7.2 years, there were no significant differences in OS and PFS between the two arms [Log rank P=0.93 and P=0.89, respectively]. Conclusions: The timing of perioperative DC chemotherapy does not affect the overall survival of patients with LAGC.
Phase I and pharmacokinetics/pharmacodynamics (PK/PD) study of MEK inhibitor, RO4987655, in Japanese patients with advanced solid tumors.
Authors: Yamada Yasuhide , Nokihara Hiroshi , Yamamoto Noboru , Fujiwara Yutaka , Tamura Yosuke , Wakui Hiroshi , Honda Kazunori , Nakamichi Shinji , Asahina Hajime , Tanabe Yuko , Kitazono Satoru , Mizugaki Hidenori , Yamazaki Naoya , Suzuki Shigenobu , Sasaki Junichi , Matsuoka Mieko , Tamura Tomohide 
Published: February 2017

116 Background: RO4987655 is an oral and selective inhibitor of MEK, a key enzyme of the MAPK signaling pathway. This was a phase I, non-randomized, open-label, dose-escalation study in Japanese patients (pts) with advanced solid tumors. Primary objectives were determination of maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs), safety evaluation and PK analysis. Secondary objectives were PD analysis and exploratory analysis of RO4987655’s anti-tumor activity according to the RECIST 1.0 criteria. Methods: Patients received an oral single dose of RO4987655 (1, 2, 4, 5, and 6.5 mg) (Cycle 0) followed by continuous once daily dosing (QD, 1, 2, and 4 mg/day) then twice daily dosing (4, 5, and 6.5 mg BID, total daily dose: 8, 10 and 13 mg/day) in 28-day cycles. A 3 + 3 dose-escalation design was used. Blood samples for PK analysis were collected in Cycle 0 (Day 1, 2 and 3) and in Cycle 1 (Day 1, 8, 15 and 22). PD was evaluated by pERK inhibition in peripheral blood mononuclear cells (PBMCs) using FACS analysis. Results: In dose-escalation, 25 pts were enrolled. After the MTD was defined, 6 pts were added to the MTD dose for further confirmation of safety profile. Tumor types included esophageal (n=8), colorectal (n=8) and non-small cell lung cancer (NSCLC) (n=4). MTD was defined as 8 mg/day due to 4 DLTs of Grade 3 creatine phosphokinase (CPK) elevation. Most commonly related adverse events included dermatitis acneiform, CPK elevation, and eye disorders, particularly macular edema and visual impairment. Plasma concentration of RO4987655 appeared to increase in a dose-proportional manner with a plasma half-life of 4.32 to 21.1 hours. After multiple dose administration, steady-state conditions were reached by Cycle 1 Day 8. The inhibitory effects of RO4987655 on pERK in PBMCs increased in a dose-dependent manner. An esophageal cancer pt confirmed partial response with over 50% shrinkage and 6 pts including NSCLC noted as stable disease ≥16 weeks by independent assessment. Conclusions: RO4987655 is tolerable with a favorable PK/PD correlation in Japanese pts with advanced solid tumors. Exploratory analysis of biomarker is ongoing. Clinical trial information: JapicCTI-111490.
Adjuvant chemotherapy for elderly patients (age 70 or older) with gastric cancer after gastrectomy with D2 dissection: A single-center experience.
Authors: Jo Jae-Cheol , Baek Jin Ho , Koh Su-Jin , Kim Gyu Yeol , Cho Hong Rae , Kim Hawk , Park Jae Hoo , Min Young Joo 
Published: February 2017

117 Background: Adjuvant chemotherapy for gastric cancer after gastrectomy with D2 dissection can be recommended. However, there are limited data of survival benefit in the elderly. We sought to investigate the use of adjuvant chemotherapy for patient ≥70 years old with stage II or III gastric cancer and identify its impact on survival. Methods: Patient ≥70 diagnosed with stage II or III gastric cancer at the Ulsan University Hospital from 2008-2012 were identified. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, chemotherapy used, toxicity, and survival. Results: A total of 277 patients ≥70 years old underwent gastrectomy with D2 dissection from 2008-2012. Of these, 94 patients were pathologically diagnosed as stage II or III gastric cancer. Among the 94 patients, 58.5% of patients (n=55) received adjuvant chemotherapy and 39 patients received regular check-up without chemotherapy. Fluoropyrimidine alone regimens including TS-1 (n=26) and Didox (n=22) were more commonly used compared with fluroropyrimidine-platinum combination regimens (n=7). With median follow-up of 30.9 (range, 0.8-65.5 months), the median relapse-free survival (RFS) of patients with adjuvant chemotherapy or regular follow-up only was 39.1 and 26.1 months (P = 0.027). Multivariate analysis revealed that the adjuvant chemotherapy was associated with longer RFS (hazard ratio 0.51; 95% confidence interval 0.27 – 0.98). There was a trend toward improved overall survival (OS) in the adjuvant chemotherapy group, with a median OS of 51.2 months compared with that of 44.5 months in the regular follow-up only group (P= 0.242). Toxicities in adjuvant chemotherapy were generally tolerated. Conclusions: In elderly patients (aged 70 or older) with stage II or III gastric cancer after gastrectomy with D2 dissection, adjuvant chemotherapy may carry a potential survival benefit for those who receive it. Further well-designed prospective studies are needed to confirm these finding.
Impact of sarcopenia on long-term prognosis of patients with esophageal cancer after surgery.
Authors: Hayashi Tsutomu , Ozawa Soji , Kamachi Kenichi , Kazuno Akihito , Ito Eisuke , Chino Osamu , Shimada Hideo , Makuuchi Hiroyasu 
Published: February 2017

118 Background: Emerging evidence suggests that sarcopenia might have an adverse impact on the survival of patients with cancer. We herein investigated the impact of sarcopenia on the long-term outcome of patients with esophageal cancer after curative surgery by analyzing the muscle cross-sectional area using computed tomography (CT). Methods: Sarcopenia was assessed in 204 patients undergoing a macroscopic curative esophagectomy for the resection of esophageal cancer between January 2005, and December 2008 at Tokai University Hospital by measuring the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on CT images obtained before surgery. The measured total psoas area (TPA) was normalized according to the patient’s height. Sarcopenia was defined as a TPA of ≤525 mm/m2 for men, and ≤375 mm/m2 for women. The impact of sarcopenia was assessed after controlling for clinical factors using multivariate modeling. Results: The median follow-up period was 60 months. The median patient age was 64 years; 184 (90%) patients were male and 20 (10%) were female. The median TPA was 580 mm/m2 for the men and 386 mm/m2 for the women. Sixty-nine (34%) patients had sarcopenia (TPA ≤525 mm/m2 for men, 375 mm/m2 for women ). The overall five-year survival rates were 33% for the patients with sarcopenia, and 66% for those without sarcopenia. In a multivariate analysis, a low body mass index (BMI ≤ 18.5 kg/m2; hazard ratio [HR], 1.87 [P = 0.028]), pathological stage of disease (HR for stage I, 1.587 in stage II [P = 0.219], 4.146 in stage III [P < 0.001], and 6.712 in stage IV [P < 0.001]), tumor location (HR of upper thoracic for middle and lower thoracic, 2.350 [P = 0.002]), and sarcopenia (HR, 1.858 [P= 0.006]) were independently associated with the overall mortality. Conclusions: Sarcopenia is associated with an increased risk of overall mortality in esophageal cancer after curative surgery independent of tumor-specific factors and the BMI. The development of effective interventions for sarcopenia warrants further study to improve the prognosis of patients with esophageal cancer.
Gastric cancer new nomograms based on preoperative clinical prognostic factors.
Authors: Bando Etsuro , Kattan Michael W. , Ohori Makoto , Tokunaga Masanori , Tanizawa Yutaka , Kawamura Taiichi , Terashima Masanori 
Published: February 2017

12 Background: Nomogram has been developed and shown to be more accurate than the conventional staging systems for predicting prognosis in gastric cancer patients. Preoperative clinical staging is a primary measure with which therapeutic strategies for gastric cancer is determined. While many reports have been published on the relationship between nomogram based on pathologic factors and survival outcomes, there were no reports of developing nomogram based on preoperative clinical factors. The purpose of this study was to firstly build a specific nomograms based on preoperative clinical prognosticators for predicting overall survival (OS) and disease-specific survival (DSS) in patients with primary gastric cancer for choosing accurate therapy preoperatively. Methods: We included patients with primary 2,807 gastric cancer patients, who had not been undergone prior chemotherapy, between 2002 and 2010. The priori chosen pre-operative prognostic covariates were sex, age, tumor site, tumor size, histologic subtype obtained by endoscopy, endoscopic macroscopic appearance, tumor depth, numbers of positive nodes and distant metastases on CT scan, and serum concentration of CEA/CA19-9. Internal validation was performed by applying the nomograms to the patients of an internal cohort calculated by bootstrap re-sampling method. The model's discriminative ability was estimated by means of Harrell’s C statistics. Results: At a median follow-up of 57 months, 612 deaths and 523 cancer-related deaths were recorded. Five-year OS and DSS rates were 64.3% and 72.4%. In Cox regression, depth and nodal involvement is the most powerful independent prognostic factors. And type4 is identified negative prognosticators. Sex and serum tumor markers have little effectiveness for survival outcome. The bootstrap-corrected Harrell’s C statistics for OS and DSS of our nomograms were 0.852 and 0.880, which was higher than that of TNM seventh edition (C=0.826, 0.822) or that of sixth edition (C=0.822, 0.801). Conclusions: These nomograms accurately predict OS and DSS of Japanese gastric cancer patients pre-operatively. Worldwide external validation should be necessary for practical use of our nomograms instead of TNM classification.
Safety, tolerability, and pharmacokinetics (PK) of rilotumumab in Japanese patients (pts) with advanced solid tumors.
Authors: Doi Toshihiko , Tang Rui , Zhang Yilong , Loh Elwyn , Lizambri Richard , Yasui Hirofumi 
Published: February 2017

130 Background: Rilotumumab (R) is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor, the only known MET receptor ligand. The MET pathway has been identified as a potentially useful target for therapeutic blockade in oncology. R has been studied in multiple phase 2 trials either as monotherapy or combination therapy, including a phase 2 trial in gastric cancer combining R with epirubicin, cisplatin, and capecitabine. A phase 1 study was done to evaluate the safety, tolerability, and PK of R in Japanese pts. Methods: An open-label, dose-escalation study was performed with R at 10 mg/kg (Cohort 1A), escalating to 20 mg/kg (Cohort 1B) if no dose-limiting toxicities (DLTs) were observed. Key eligibility criteria were Japanese pts with unresectable locally advanced or metastatic carcinoma, age ≥ 20 yr, ECOG ≤ 1, and refractory to standard treatment (tx). Pts received R as an intravenous infusion on days 1 and 15 of each 28-day cycle, except for cycle 1 in which the day 15 dose was skipped to facilitate PK analysis. DLTs were evaluated in cycle 1. Results: A total of 9 pts were enrolled (1A, n = 3; 1B, n = 6). No DLTs were noted. As of 17 April 13, tx-emergent AEs were reported in 89% of pts. Tx-emergent AEs occurring in > 1 pt overall were vomiting (33%), diarrhea (22%), decreased hemoglobin (22%), hypoalbuminemia (22%), and nausea (22%). One grade 3 tx-emergent AE was observed (decreased hemoglobin; 10 mg/kg). Tx-related AEs were reported in 56% of pts. One grade ≥ 2 tx-related AE was observed (hypoalbuminemia; 20 mg/kg). 8 pts discontinued R due to disease progression; 1 pt remained on the investigational product. Mean exposure of R (Cmax and AUC) appeared to be doubled as dose increased from 10 to 20 mg/kg. The estimated mean CL was approximately 0.2 mL/hr/kg in both cohorts, suggesting a linear PK from 10 to 20 mg/kg. The terminal half-life of R was about 15 days. Conclusions: R monotherapy had an acceptable safety profile in Japanese pts with advanced solid tumors. These phase 1 safety and PK data support the further evaluation of R combined with chemotherapy in Japanese pts with MET-positive metastatic gastric cancer. Clinical trial information: NCT01791374.
Long-term follow-up of advanced gastric cancer patients who achieved a pathologic complete response with neoadjuvant chemotherapy.
Authors: Cho Haruhiko , Yoshikawa Takaki 
Published: February 2017

133 Background: Adjuvant chemotherapy (AC) after D2 gastrectomy has become a standard treatment for stage 2/3 gastric cancer in Japan and Korea; however, the results remain unsatisfactory due to insufficient risk reduction in patients with stage 3 disease and low compliance. Although the administration of neoadjuvant chemotherapy (NAC) is a promising approach associated with a high rate of compliance and a downstage effect, the long-term survival benefits of this modality are unclear. Moreover, the impact of the pathological response on survival has not been evaluated. Based on the hypothesis that the pathological response grade is associated with survival, we conducted a search for reports of a pathological complete response (pCR) obtained with NAC. Methods: A total of 27 gastric cancer patients who achieved a pCR following NAC therapy were identified using PubMed and the Japanese medical search engine “Ichu-shi,” with the search words “gastric cancer,” “NAC,” and “pCR.” A questionnaire regarding the patients’ prognoses was posted in 23 institutions in Japan in July 2013. Results: Answers regarding 22 patients were obtained from 20 institutions. The subjects included 13 males and nine females. The mean age was 67.5 years. Tumors with stage 3/4 (95.4%: 21/22) and a diffuse-type histology (61.9%: 13/21) were dominant. S1/CDDP was the most frequently selected NAC regimen. A total of 77.2% (17/22) of the patients required combined resection of adjacent organs, and all patients underwent R0 resection and D2 lymphadenectomy. At present, 86.3% (19/22) of the patients are alive without recurrence; none of the ten patients who received postoperative AC demonstrated any recurrence, while three of twelve patients who did not receive postoperative AC developed recurrence, and two patients died of the disease after surgery (at 71 months and nine months, respectively). The overall and recurrence-free survival rates at three/five years were 95.5%/85.1% and 90.9%/75.1%, respectively. Conclusions: Patients with gastric cancer who achieve a pCR with NAC are rare; however, their prognoses are excellent. It is therefore important to develop a NAC regimen focusing on a high pCR rate.