http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Charles S. Fuchs,Kei Muro,Jiri Tomasek,Eric Van Cutsem,조재용,오상철,Howard Safran,György Bodoky,Ian Chau,Yasuhiro Shimada,Salah-Eddin Al-Batran,Rodolfo Passalacqua,Atsushi Ohtsu,Michael Emig,David Ferry,Ku 대한위암학회 2017 Journal of gastric cancer Vol.17 No.2
The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Fuchs, Charles S.,Muro, Kei,Tomasek, Jiri,Van Cutsem, Eric,Cho, Jae Yong,Oh, Sang-Cheul,Safran, Howard,Bodoky, Gyorgy,Chau, Ian,Shimada, Yasuhiro,Al-Batran, Salah-Eddin,Passalacqua, Rodolfo,Ohtsu, Ats The Korean Gastric Cancer Association 2017 Journal of gastric cancer Vol.17 No.2
Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Tabernero, Josep,Ohtsu, Atsushi,Muro, Kei,Van Cutsem, Eric,Oh, Sang Cheul,Bodoky, Gyorgy,Shimada, Yasuhiro,Hironaka, Shuichi,Ajani, Jaffer A.,Tomasek, Jiri,Safran, Howard,Chandrawansa, Kumari,Hsu, Yan American Association for Cancer Research 2017 Molecular cancer therapeutics Vol.16 No.10
<P>Ramucirumab is an IgG1 monoclonal antibody specific for the vascular endothelial growth factor receptor-2. Ramucirumab, 8 mg/kg every 2 weeks, administered as monotherapy (REGARD) or in combination with paclitaxel (RAINBOW), was safe and effective in patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer. We evaluated exposure-efficacy and exposure-safety relationships of ramucirumab from two randomized, placebo-controlled phase III trials. Sparse pharmacokinetic samples were collected, and a population pharmacokinetic analysis was conducted to predict ramucirumab minimumtrough concentration at steady state (C-min,C-ss). Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the ramucirumab exposure (C-min,C-ss)-efficacy relationship to overall survival (OS) and progression-free survival (PFS). Logistic regression analyses were used to evaluate exposure-safety relationships. Analyses included 321 ramucirumab + paclitaxel and 335 placebo + paclitaxel patients from RAINBOW and 72 ramucirumab and 35 placebo patients from REGARD. Exposure-efficacy analysis showed ramucirumab C-min,C-ss was a significant predictor of OS and PFS in both trials. Higher ramucirumab exposure was associated with longer OS and PFS. In RAINBOW, grade >= 3 hypertension, leukopenia, and neutropenia, but not febrile neutropenia, significantly correlated with Cmin, ss, with increased exposure leading to increased incidence. Exploratory exposure-response analyses suggest a positive relationship between efficacy and ramucirumab exposure with manageable toxicities at exposures generated from a dose of 8 mg/kg ramucirumab given every 2 weeks for patients with advanced gastric/GEJ cancer. These findings suggest an opportunity to further optimize benefit versus risk profiles of ramucirumab treatment in patients with gastric/GEJ cancer. (C) 2017 AACR.</P>