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Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study.
Hong, X, Song, Y, Huang, H, Bai, B, Zhang, H, Ke, X, Shi, Y, Zhu, J, Lu, G, Liebscher, S, et al
Targeted oncology. 2019;(2):149-158
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Abstract
BACKGROUND Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. OBJECTIVE As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL. PATIENTS AND METHODS In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1-14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m2/week for 6 weeks in 7-week cycles (with vitamin B12/folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%). RESULTS The study's primary objective was met: ORR (95% CI) was 52% (40-64%) (p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3-14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1-8.1) months and 18.0 (10.4-NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%]). CONCLUSIONS These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03349333.
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Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial.
Motzer, RJ, Porta, C, Vogelzang, NJ, Sternberg, CN, Szczylik, C, Zolnierek, J, Kollmannsberger, C, Rha, SY, Bjarnason, GA, Melichar, B, et al
The Lancet. Oncology. 2014;(3):286-96
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BACKGROUND An unmet medical need exists for patients with metastatic renal cell carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. Fibroblast growth factor (FGF) pathway activation has been proposed as a mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors. We therefore compared dovitinib with sorafenib as third-line targeted therapies in patients with metastatic renal cell carcinoma. METHODS In this multicentre phase 3 study, patients with clear cell metastatic renal cell carcinoma who received one previous VEGF-targeted therapy and one previous mTOR inhibitor were randomly assigned through an interactive voice and web response system to receive open-label dovitinib (500 mg orally according to a 5-days-on and 2-days-off schedule) or sorafenib (400 mg orally twice daily) in a 1:1 ratio. Randomisation was stratified by risk group and region. The primary endpoint was progression-free survival (PFS) assessed by masked central review. Efficacy was assessed in all patients who were randomly assigned and safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01223027. FINDINGS 284 patients were randomly assigned to the dovitinib group and 286 to the sorafenib group. Median follow-up was 11·3 months (IQR 7·9-14·6). Median PFS was 3·7 months (95% CI 3·5-3·9) in the dovitinib group and 3·6 months (3·5-3·7) in the sorafenib group (hazard ratio 0·86, 95% CI 0·72-1·04; one-sided p=0·063). 280 patients in the dovitinib group and 284 in the sorafenib group received at least one dose of study drug. Common grade 3 or 4 adverse events included hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), fatigue (24 [8%]), dyspnoea (21 [7%]), and palmar-plantar erythrodysaesthesia (18 [6%]) in the sorafenib group. The most common serious adverse event was dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, respectively). INTERPRETATION Dovitinib showed activity, but this was no better than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGF-targeted therapies and mTOR inhibitors. This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting. FUNDING Novartis Pharmaceuticals Corporation.
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[Radioactive seed implantation for the treatment of mediastinal malignant tumors and lymph node metastases in 43 cases].
Luo, L, Wang, H, Ma, H, Cai, C, Zhang, J, Zou, H
Zhongguo fei ai za zhi = Chinese journal of lung cancer. 2011;(12):933-7
Abstract
BACKGROUND AND OBJECTIVE The locations of mediastinal malignant tumor lesions are deep and occult, and are close to the pericardium, trachea, or major vessels. Therefore, the possibility of surgical resection is slim, and cryoablation and thermal ablation are restricted. In current study, image and life quality data were compared before and after 125I seeding therapy to investigate its safety and clinical effects. METHODS From July 2010 to July 2011, a 43-patient follow-up of pathologically confirmed cancers, including 21 cases of primary mediastinal squamous lung cancer, 9 cases of primary esophagus cancer, and 13 cases of lymph node metastases were completed. Among these, 18 cases presented with tracheal stenosis >50%, 9 cases had esophageal obstruction, and 9 cases had superior vena cava reflux disorder. Each lesion was implanted with 10 to 60 pieces of 125I particles, with an average of 30.79±14.23. CT data at 2, 4, 6, and 12 months after therapy were obtained to evaluate the local lesion outcome. The quality of life of the patients as well as survival data was also recorded. RESULTS The overall success rate of the operation was 100%. The longest time of follow-up was 12 months. At 6 months, 37 patients were alive, and the half-year survival rate was 85.0%. In terms of local lesions, 30 cases of PR and 7 cases of NC were found. The clinical effective rate was 81.08%, and the clinical beneficial rate was 100%. At 12 months after therapy, 31 patients were alive, and the one-year survival rate was 60.5%. In terms of local lesions, 16 cases of CR, 7 cases of PR, 2 cases of NC, and 6 cases of PD were found. The clinical effective rate was 74.19%, and the clinical beneficial rate was 80.65%. The KPS score increased after the treatment (P=0.000). Three cases of pneumothorax presented after treatment, and no severe complications, such as vessel, trachea, recurrent laryngeal nerve, or pericardiocentesis injuries, were found. CONCLUSIONS Radiation seed implantation in mediastinal malignant tumors is a relatively safe technique with high success rate, considerable efficacy, and clear clinical value in advanced cancer treatment.
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Relationship between urinary cysteinyl leukotriene E4 levels and clinical response to antileukotriene treatment in patients with asthma.
Cai, C, Yang, J, Hu, S, Zhou, M, Guo, W
Lung. 2007;(2):105-12
Abstract
The aim of this study was to investigate and identify the relationship between urinary cysteinyl leukotriene E(4) levels and clinical response to antileukotriene treatment in patients with asthma. Forty-eight patients with stable mild to moderate asthma were treated with montelukast in a four-week trail. Asthmatic symptom score, beta(2)-agonist usage, percentage of eosinophil, total serum IgE concentration, forced expiratory volume in the first second (FEV(1)), peak expiratory flow rate (PEFR), and urinary leukotriene E(4) (uLTE(4)) were measured before and after treatment. Clinical response was assessed by the improvement of asthma symptom scores, beta(2)-agonist usage, and FEV(1). Responders were defined as patients who had to fit the following three criteria: a reduction of more than 20% in mean symptom score; a reduction of more than 20% in beta(2)-agonist usage, and a mean improvement of FEV(1) of more than 10% from baseline value. Others were classified as nonresponders. Logistic analysis was used to access the various clinical factors correlated with the clinical response. There were 25 responders and 23 nonresponders. The mean uLTE(4) level from the responders was higher than that from the nonresponders (224.5 +/- 34.4 vs. 175.3 +/- 37.1 pg/mg creatinine, p < 0.05). There was a significant correlation between the clinical response and the uLTE(4) level but not demographic features, percentage of eosinophils, serum IgE concentration, or spirometry (p > 0.05). Subjects with a uLTE(4) level of ≥ 200 pg/mg creatinine were 3.5 times more likely to respond to montelukast than those with less than 200 pg/mg creatinine (95% confidence interval [CI] = 1.7-15.8). The uLTE(4) level is closely correlated with antileukotriene treatment. uLTE(4) is a good biomarker for selecting this drug to treat asthma.