bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, double-blind, placebo-controlled phase II study of AMG 386 in combination with cisplatin and capecitabine (CX) in patients (pts) with metastatic gastroesophageal adenocarcinoma.
Authors: Eatock M. M. , Szanto J. , Tebbutt N. C. , Bampton C. L. , Strickland A. H. , Valladares Ayerbes M. , Nanayakkara N. , Sun Y. , Adewoye A. H. , Bodoky G. 
Published: February 2017

66 Background: AMG 386, a first-in-class investigational peptide-Fc fusion protein (peptibody), blocks angiogenesis via inhibiting the interaction between angiopoietins-1 and -2 and the Tie2 receptor. We evaluated the efficacy and tolerability of AMG 386 or placebo plus CX in the first-line treatment of metastatic gastroesophageal adenocarcinoma. Methods: Pts with confirmed metastatic adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus were randomized 1:1:1 to receive CX (cisplatin, 80 mg/m2 IV Q3W; capecitabine, 1,000 mg/m2 orally BID for 14 days Q3W) plus AMG 386 10 mg/kg (Arm A), 3 mg/kg (Arm B), or placebo (Arm C) IV QW. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR; in pts with measurable disease), adverse events (AEs), and pharmacokinetics (PK). Results: 171 pts were randomized (Arm A/B/C, n = 56/59/56). Efficacy results are summarized in the table. The incidence of grade ≥ 3 AEs in Arms A/B/C was 80/84/75%. Serious AEs occurred in 73/60/47% and serious AEs grade ≥ 3 in 66/60/43% of pts. AEs in Arms A/B/C included abdominal pain (30/40/17%; grade ≥ 3, 18/3/4%), peripheral edema (13/29/6%; grade ≥ 3, 0/2/0%), venous thromboembolic events (20/22/19%; grade ≥ 3, 20/19/17%), and pulmonary embolism (9/3/15%; grade ≥ 3, 9/2/13%). Median AMG 386 Cmax and Cmin values at steady state after CX coadministration were dose-proportional. Coadministration with CX did not markedly affect AMG 386 exposure. Conclusions: In this study, AMG 386 plus CX did not significantly improve PFS or ORR over placebo plus CX in this patient population. The toxicity of the combination of AMG 386 plus CX, compared with placebo, was greater but manageable. No unexpected AEs occurred. [Table: see text] [Table: see text]
A randomized controlled phase III trial to evaluate the effect of preoperative enteral immunonutrition on the surgical site infection after total gastrectomy (OGSG0507).
Authors: Kimura Y. , Tsujinaka T. , Fujitani K. , Fujita J. , Miyashiro I. , Imamura H. , Kobayashi K. , Kurokawa Y. , Shimokawa T. , Furukawa H. ,   Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG)
Published: February 2017

74 Background: To investigate the effect of preoperative enteral immunonutrion on the incidence of surgical site infection (SSI) after total gastrectomy for gastric cancer, we conducted a prospective randomized controlled trial. Methods: Eligibility criteria included: (1) histologically proven adenocarcinoma of stomach, (2) scheduled total gastrectomy, (3) aged less than 80 years, (4) not malnourished, (5) possible to ingest liquid diet, (6) written informed consent. Eligible patients (pts) wereassigned to the immunonutrition (I) group or the control (C) group. In the C group pts freely accessed to regular diet until surgery. In the I group, pts were supplemented with 1,000 ml/day of immunonutrient enriched with arginine, omega-3 fatty acids and RNA (Impact) in addition to the regular diet for 5 days before surgery. The primary endpoint was the incidence of SSI and the secondary endpoints were other infectious complications and serum CRP level on POD 3 or 4. Results: From 02/2004 to 12/2009, 240 gastric cancer patients (pts) who underwent gastric surgery were enrolled. 125 pts assigned to the I group and 115 pts assigned to the C group. Age, sex, body weight, serum albumin and general nutritional status were well balanced between the two groups. 223 pts underwent total gastrectomy, 6 pts proximal gastrectomy, 4 pts distal gastrectomy, and 7 pts simple laparotomy. In terms of tumor status, there were no significant difference between the groups in histological type, T stage, and lymph node metastasis. 104 of 125 pts assigned to the I group tolerated a daily intake 1,000 ml of Impact for 5 days. The incidence of SSI was 26 (20.8%) in the I group and 24 (20.9%) in the C group (R.R: 1.00, 95% C.I: 0.61-1.63). Postoperative morbidity was 36 (28.8%) in the I group and 30 (26.1%) in the C group. There was no difference in days of hospital stay after surgery between the groups. Conclusions: The oral administration of immunonutrient for 5 days before surgery did not contributed to the reduction of infectious complications after total gastrectomy in gastric cancer pts. No significant financial relationships to disclose.
Patterns of radiotherapy practice in the management of gastric cancer: Preliminary findings from the Quality Research in Radiation Oncology (QRRO) GI Committee process surveys.
Authors: Goodman K. A. , Khalid N. , Kachnic L. A. , Minsky B. D. , Crozier C. , Owen J. B. , Wilson J. F. , Thomas C. R. 
Published: February 2017

77 Background: The specific aim of the ACR QRRO survey was to determine the national patterns of radiotherapy (RT) practice in patients (pts) treated for stage IB–IV (non-metastatic) gastric cancer (GC). Methods: A National Process Survey was conducted from randomly selected U.S. RT facilities to assess demographics, staging, geographic region, practice setting, and treatment through retrospective on-site record review of eligible GC cases treated from 2005-2007. Three clinical performance measures (CPMs): 1) use of CT-based treatment planning; 2) use of dose volume histograms (DVHs) to evaluate RT dose to the kidneys and liver; 3) completion of RT within the prescribed time frame were assessed. Three emerging quality indicators: 1) use of intensity modulated RT (IMRT); 2) use of image-guided tools (IGRT), other than CT, for RT target delineation; 3) use of preop RT were also assessed. Results: CPMs were computed on data collected through Aug, 2010 for 250 eligible pts at 45 institutions. Median age was 62 years; 66% male; 60% Caucasian. 13% were AJCC 2002 stage I, 29% II, 32% IIIA, 10% IIIB and 12% IV. Most pts (43%) were treated at academic centers with 32% at large non-academic centers and 25% medium-small facilities. Almost all (99.5%) pts underwent CT-based planning and 75% had DVHs to evaluate normal tissue doses to the kidneys and liver. 70% completed RT within the prescribed time frame. IMRT and IGRT were used in 22% and 17% of pts, respectively. IGRT techniques included: PET (n = 20), MRI (n = 1), respiratory gating and/or 4D-CT (n = 22) and on-board imaging (n = 10). 19% of pts received preop RT. Conclusions: Preliminary findings from QRRO's analysis of radiation practice patterns for non-metastatic gastric cancer indicate widespread adoption of CT-based planning with the use of DVHs to evaluate normal tissue doses. Moreover, most pts completed adjuvant RT in the prescribed time frame. Emerging RT techniques such as IMRT and IGRT were not routinely incorporated into clinical practice during the evaluated time period. These data will serve as a benchmark for future QRRO gastric cancer surveys. No significant financial relationships to disclose.
Onset of CT scan morphological changes in metastatic lesions and associated responses in gastric patients treated with telatinib.
Authors: Bhosale P. , Ajani J. A. , Baker J. S. , Whiteside M. , Castillo J. , Kunkel L. A. 
Published: February 2017

81 Background: Response to the antiangiogenic agent, bevacizumab, by CT has been associated with a unique morphologic change in liver metastasis (mets) where heterogeneous attenuation, variable degree of enhancement and ill-defined borders before treatment transform into homogeneous, hypoattenuating lesions with well defined borders, mimicking a cyst. CT-based morphologic criteria in colorectal cancer (CRC) had a statistically significant association with pathologic response and overall survival, (Chun, JAMA 2009). The CT changes likely reflect the replacement of mets by fibroconnective tissue rather than tumor necrosis. Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Methods: TEL0805, a Phase 2 study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Response assessments were every 2 cycles (6 weeks). The ORR in response evaluable pts was 69% (1 CR, 21 PR in 32 pts). CT films from 16/32 response evaluable pts were analyzed and reviewed by a radiologist at a single institution, 10 pts had liver mets. Results: The median onset of response was 49 days. CT changes of mets at week 6 scans included: decreased attenuation and/or a sharp interface with rapid reduction of mets (n=6); mixed response, with decreased attenuation but persistent borders, and/or slight increase in mets followed by onset of response week 12 (n=3), and PD (n=1). CT changes correlate with durable responses. Conclusions: Telatinib + XP produces rapid onset of tumor response with morphologic CT changes in gastric cancer liver mets similar to those observed in CRC pts with bevacizumab, consistent with antiangiogenic activity. Further analyses in a randomized setting to correlate CT morphologic response with survival are planned. [Table: see text]
Efficacy of adjuvant chemotherapy with S-1 in patients with positive peritoneal cytology (CY1) who underwent R1 surgery.
Authors: Terashima M. , Bando E. , Tokunaga M. , Tanizawa Y. , Kawamura T. , Kondo J. , Kinugasa Y. , Kanemoto H. , Uesaka K. 
Published: February 2017

84 Background: In recent TNM classification, positive peritoneal cytology (CY1) is regarded as M1 disease and classified into stage IV. However, the prognosis of the CY1 patients underwent R1 surgery (microscopic residual tumor) is considered to be relatively better than those underwent R2 surgery (macroscopic residual tumor). Adjuvant chemotherapy with S-1 had demonstrated significant survival benefit in stage II and III gastric cancer in Japan. However, the efficacy of adjuvant S-1 in patients with relatively more advanced stage had not been investigated. Therefore, we investigated the efficacy of adjuvant chemotherapy with S-1 in CY1 patients underwent R1 surgery. Methods: Among the 2,202 patients with gastric cancer treated at our department between September 2002 and July 2009, a total of 105 patients with CY1 and underwent R1 surgery were included in this study. Clinocopathological features and survival were retrospectively analyzed using prospectively registered data base system. Results: There were 64 male and 41 female patients. The median age was 61 years old. Eighty-five patients had T4a or T4b tumor and 96 patients had lymph node metastasis. Seventy-eight patients had undifferentiated type of tumor. In 83 patients, adjuvant chemotherapy with S-1 had been performed. In the uni-variate analysis, only the extent of lymph node dissection (D2) and the adjuvant chemotherapy with S-1 demonstrated significant survival benefit. In multi-variable analysis using Cox proportional hazarded model, N-factor, extent of lymph node dissection (D2 vs D1), and adjuvant chemotherapy with S-1 were selected as independent prognostic factors. The median survival time and 5-year survival rate in patients underwent R1 resection with D2 lymphadenectomy and adjuvant S-1 treatment were 42 months and 46%, respectively. Conclusions: In patients with CY1 and underwent R1 surgery, adjuvant chemotherapy with S-1 demonstrated significant survival benefit. In patients with positive peritoneal cytology without other non-curative factors, D2 lymph node dissection and adjuvant chemotherapy using S-1 is recommended. No significant financial relationships to disclose.
A global, multicenter phase II trial of lapatinib plus capecitabine in gastric cancer.
Authors: Pishvaian M. , Sakaeva D. , Hsieh R. K. , Rha S. Y. , Caderillo-Ruiz G. , Miller W. H. , Kemner A. M. , Nagarwala Y. M. , Zhang W. , Lenz H. 
Published: February 2017

88 Background: Advanced gastric cancer (GC) is an incurable disease. HER2 overexpression has been reportedin 6%–35% of gastric and gastroesophageal tumors, whereas the EGFR is upregulated in about 18%–28%. Clinical studies confirm that targeting HER2 in combination with chemotherapy is an effective strategy, achieving a median survival of ∼13.5 mos. Lapatinib, a dual tyrosine kinase inhibitor of HER2 and the EGFR, inhibits tumor growth and modulates expression of fluoropyrimidine-targeting genes. LPT109747 is an international, multicenter phase II study investigating the combination of lapatinib + capecitabine in patients with advanced gastric or gastroesophageal junction adenocarcinoma. Methods: Primary endpoints of the study included clinical response rate, 5 mo PFS and mRNA and protein expression levels of genes involved in the 5-FU and HER2 pathway. HER2 overexpression was not required at study entry. Oral lapatinib was administered (1,250 mg/d, continuously) during a monotherapy run-in period (day -7 to 0) and in combination with oral capecitabine (1,000 mg/m2 BID, 14 of 21 days). Patients were treated until disease progression (PD) or study withdrawal. Biopsies were performed on days -7 and 0. Safety was assessed every 3 weeks and response every 6 weeks by RECIST. Results: Sixty-seven patients were included in the current analysis: 25% female, 75% male; 51% Caucasian, 45% Asian; median age 60 y (range: 22-89 y); 75% GC, 25% GEJ. All 67 patients were evaluable for response. The overall response rate was 22.4% (16.4% confirmed). 45% of patients had stable disease, and 24% had PD. No complete responses were observed. PD or death at < 5 mo was 63%. At the time of data cut off, PFS at 5 mo was 28.4% (17.3%–40.5%); median follow up was 26.4 weeks (CI: 22.1; 55.9); 39% of patients remain in follow up. Most frequent grade 3/4 events were anemia (13%), hand-foot syndrome (12%), decreased appetite (10%), and nausea (9%). Conclusions: The combination of lapatinib + capecitabine shows promising efficacy and is well tolerated as 1st line treatment for advanced GC. An analysis of biomarker data may help identify who may benefit most from this regimen. [Table: see text]
An integrated analysis of two phase II trials (JCOG0001 and JCOG0405) of preoperative chemotherapy followed by D3 gastrectomy for gastric cancer (GC) with extensive lymph node metastasis (ELM).
Authors: Tsuburaya A. , Katayama H. , Mizusawa J. , Nakamura K. , Katai H. , Imamura H. , Nashimoto A. , Fukushima N. , Sano T. , Sasako M. ,   The Gastric Cancer Surgical Study Group of JCOG
Published: February 2017

90 Background: GC with ELM (bulky N2 metastasis and / or para-aortic lymph node metastases [PAN]) is commonly regarded unresectable, while in JCOG combined modality treatment has been tested since 2000 (JCOG0001 and JCOG0405). Both trials met their primary endpoints (i.e., 3 year-survival of 27.3% in JCOG0001 and R0 resection of 82.4% in JCOG0405). The survival and the toxicity profile were quite different between the trials despite the similar eligibility with an outstanding 3-year survival of 58.8% in JCOG0405. This study is conducted to explore if survival is still better in JCOG0405 after adjusting baseline factors and if there is a subset of patients (pts) who benefit more from either treatment. Methods: Eligibility criteria for both included histologically proven gastric adenocarcinoma; bulky nodal involvement around major branched arteries to the stomach and/or PAN; cM0 (except PAN); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Pts received two or three cycles of induction chemotherapy of IP: irinotecan (70 mg/m2 on day 1 and day 15) and cisplatin (80 mg/m2 on day 1) in JCOG0001, or SP: S1 (80 mg/m2 from day 1 to 21) and cisplatin (60 mg/m2 on day 8) in JCOG0405, followed by D3 gastrectomy. Multivariate analysis for overall survival adjusting baseline factors and treatment (IP/SP) was performed with a Cox regression model. Interaction tests were also carried out between baseline factors and treatment. Results: After adjusting baseline factors, SP was superior than IP for overall survival (HR=0.335: 0.184 – 0.612). There was only interaction effect between treatment and the status of lymph node metastases (bulkyN+/PAN- vs bulkyN-/PAN+ vs bulkyN+/PAN+; p=0.1306). Conclusions: SP was shown to be the favorable treatment for GC with ELM by multivariate analysis, while poor prognosis in pts having both bulky N+ and PAN+ may necessitate further treatment improvement. No significant financial relationships to disclose.
Quality of life in patients with advanced gastroesophageal (GE) adenocarcinoma treated with modified docetaxel, cisplatin, and fluorouracil (mDCF).
Authors: Smyth E. C. , Janjigian Y. Y. , Robinson E. , Sheehy E. C. , Karpenko I. , Capanu M. , Kelsen D. P. , Shah M. A. 
Published: February 2017

92 Background: Although DCF is a standard first line chemotherapy option for advanced GE adenocarcinoma, the regimen is associated with significant toxicity. Even so, time to detriment in quality of life (QoL) was significantly better with parent DCF than CF (Ajani, JCO 2007). Modified DCF (mDCF) has demonstrated less toxicity than parent DCF without compromising efficacy in two phase II studies (Shah, GI ASCO 2010; Kelsen, ASCO 2009). We report the quality of life (QoL) over time of patients receiving mDCF on these two clinical trials. Methods: Patients (pts) treated on two protocols utilizing the mDCF regimen, either alone or in combination with bevacizumab, were administered standard EORTC QoL questionnaires (QLC –C30 version 3), at baseline, 6 weeks, 3, 6, 9 and 12 months (m). Chemotherapy and QoL assessment continued until disease progression. Mean score change from baseline was assessed using Wilcoxon test. Results: 94 eligible pts have been enrolled on both studies; QoL questionnaires are available on 87 pts. 74% are male, median age 58 years (range 28-78), with baseline Karnofsky performance status of 80% (range 70-100). Patient compliance with QoL assessment was high at baseline but diminished with time; 89% of pts completed the questionnaire at baseline and 41% at 12m. There was no significant detriment in EORTC QOL scores (including global health, physical and social functioning and fatigue) during treatment with mDCF (Table). Conclusions: In patients with advanced GE cancer, we observed no detriment in QoL scores in patients receiving mDCF therapy. Specifically, physical and social functioning, fatigue, appetite, and global heath QoL scores were maintained at baseline levels during the first 6 months of therapy, and appear to improve in patients who remained on protocol therapy during the next 6 months of treatment. [Table: see text] No significant financial relationships to disclose.
A single-arm, phase II feasibility study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma.
Authors: Ryu M. , Choi Y. , Kim B. , Park Y. , Kim H. , Jung H. , Lee G. , Kim K. , Yook J. , Kang Y. 
Published: February 2017

96 Background: The aim of this study was to evaluate feasibility and safety of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in patients with potentially resectable adenocarcinoma of stomach or gastroesophageal junction. Methods: Forty-one patients with clinical stage T3-4N0M0 or T2-4N+M0 determined by CT, endoscopic ultrasonography, and laparoscopy were enrolled between DEC 2008 and MAR 2010. Gastrectomy with D2 lymph node dissection was conducted after 3 cycles of DOS chemotherapy. DOS chemotherapy consists of docetaxel 50 mg/m2 iv (day1), oxaliplatin 100 mg/m2 iv (day1), and S-1 40 mg/m2 po bid (days1-14) at 3 weeks interval. After curative gastrectomy, the patients were given 1 year of adjuvant chemotherapy with S-1 (40 mg/m2 D1-28, every 6 weeks). Results: All patients finished the planned neoadjuvant chemotherapy. Twenty-three (56%) patients achieved a partial response, and the remaining 18 patients had stable disease by CT scan after 3 cycles of DOS chemotherapy. No disease progression was observed during the neoadjuvant chemotherapy. A median 4.7 weeks (range, 4.0-7.6) after the start of the 3rd cycle of DOS chemotherapy, 39 (95%) patients underwent R0 resection with no pathologic residual disease in 4 (10%) patients. Hematologic toxicities were common including grade 4 neutropenia (32%), grade 3 thrombocytopenia (17%), and febrile neutropenia (10%). However, hematologic toxicities were generally transient and manageable. There were no grade 3 or 4 non-hematologic toxicities with frequency > 5% of patients. With all toxicities taken together, 21 (51%) patients experienced grade 3 or 4 toxicities (except grade 3 neutropenia). There was no treatment-related death, and surgical complications included only mild wound problem in 4 (10%) patients. Conclusions: In this study, neoadjuvant DOS chemotherapy could induce a sufficient down-staging and R0 resection of locally advanced gastric cancer with mild and manageable toxicities. A phase III randomized trial is planned for evaluating the benefit of neoadjuvant DOS chemotherapy in patients with locally advanced gastric cancer. [Table: see text]
Initial report of RTOG 9601, a phase III trial in prostate cancer: Effect of anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) on freedom from progression and incidence of metastatic disease in patients following radical prostatectomy (RP) with pT2-3,N0 disease and elevated PSA levels.
Authors: Shipley W. U. , Hunt D. , Lukka H. R. , Major P. , Heney N. M. , Grignon D. , Patel M. , Bahary J. , Lawton C. A. , Sandler H. M. 
Published: February 2017

1 Background: To test if long term AAT when combined with RT in these patients (pts) with prostate cancer (PC) will improve cancer control outcomes as well as overall survival (OS). Methods: Post-RP pts with pT3,N0 or with pT2,N0 (and positive margins) who have an elevated PSA were entered on a phase III, double-blinded, placebo-controlled trial of RT alone (64.8 Gy in 1.8 Gy fractions) vs RT + AAT (24 months of bicalutamide, 150mg daily) during and after RT. The primary end point is OS. Results: From 3/98 to 3/03, 771 eligible pts (median age 65) were randomized to RT + AAT (387) or RT alone (383). Pretreatment characteristics were balanced. 672 (87%) had a PSA nadir after RP of < 0.5 ng/mL. 655 (85%) had an entry PSA value of <1.6, 115 (15%) had an entry PSA of 1.6-3.9. Median follow-up was 7.1 years. Actuarial OS at 7 years was 91% for RT + AAT and 86% for RT alone. Too few primary end-point events have occurred to allow a statistical comparison between groups. Freedom from PSA progression (FFP) at 7 years was 57% for RT + AAT and 40% for RT alone (P < 0.0001); for 226 pts with GS < 7 were 63% and 50% (P<0.02), for 411 GS 7 these were 55% and 39% (P<0.0006), and for 134 GS 8-10 were 56% and 26% (P < 0.0008). The 7-yr cumulative incidence of metastatic PC was less in the RT and AAT arm, 7% vs 13% in the RT arm (p<0.041). Late grade 3-4 toxicities were similar in both arms. By category the combined grade 3-4 toxicities for RT + AAT and RT alone were: bladder 6% vs 5% bowel 2% vs 1%, cardiac 3% vs 2%. Gynecomastia (mostly grades 1-2) differed significantly, 89% vs15%. In the RT + AAT arm grade 3 was the highest liver toxicity, which occurred in 3 pts. Conclusions: The addition of 24 months of bicalutamide 150 mg daily during and after RT significantly improved FFP and reduced the incidence of metastatic PC without adding significantly to RT toxicity. The significance of benefit in OS, as well analysis of risk-stratified subsets, wait longer follow-up. No significant financial relationships to disclose.