Topic
Tolerability
About: Tolerability is a research topic. Over the lifetime, 27246 publications have been published within this topic receiving 891690 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, indicating that inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinalStromal tumors, which resist conventional chemotherapy.
Abstract: Background Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors. Methods We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed antitumor response and the safety and tolerability of the drug. Pharmacokinetics were assessed in a subgroup of patients. Results A total of 147 patients were randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79 patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had stable disease, and for technical reasons, response could not be evaluated in 7 patients (4.8 percent). No patient had a complete response to the treatment. The median duration of response had not been reached after a median follow...
4,057 citations
Memorial Sloan Kettering Cancer Center1, Thomas Jefferson University2, Queen Mary University of London3, Netherlands Cancer Institute4, New York University5, University of Milan6, MedStar Georgetown University Hospital7, University of Chicago8, University of Paris-Sud9, Stanford University10, Technische Universität München11, Cleveland Clinic12, Mayo Clinic13, Icahn School of Medicine at Mount Sinai14, Yale University15, University of Navarra16, Sarah Cannon Research Institute17, Ottawa Hospital Research Institute18, Harvard University19, Genentech20, Foundation Medicine21, University of Virginia22
TL;DR: Treatment with atezolizumab resulted in a significantly improved RECIST v1.1 response rate, compared with a historical control overall response rate of 10%, and Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolediazepine.
2,934 citations
University of Navarra1, University of Hong Kong2, Kindai University3, National Taiwan University4, Seoul National University Hospital5, Goethe University Frankfurt6, University of Michigan7, Royal Free Hospital8, Asan Medical Center9, The Chinese University of Hong Kong10, Johns Hopkins University11, Bristol-Myers Squibb12, Chartered Institute of Management Accountants13
TL;DR: Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma, and safety and tolerability for the escalation phase and objective response rate were primary endpoints.
2,908 citations
TL;DR: Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in patients with pretreated advanced non-small-cell lung cancer.
Abstract: Purpose: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non–small-cell lung cancer (NSCLC). Patients and Methods: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily. Results: Efficacy was similar for the 250- and 500-mg/d groups. Objective tumor response rates were 18.4% (95% confidence interval [CI], 11.5 to 27.3) and 19.0% (95% CI, 12.1 to 27.9); among evaluable patients, symptom improvement rates were 40.3% (95% CI, 28.5 to 53.0) and 37.0% (95% CI, 26.0 to 49.1); median progression-free survival times were 2.7 and 2.8 months; and median overall survival times were 7.6 and 8....
2,885 citations
TL;DR: Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity, and tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.
Abstract: Purpose Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti‐PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. Patients and Methods Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrateresistant prostate cancer, non‐small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti‐PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. Results Anti‐PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti‐PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of 70% of PD-1 molecules on circulating T cells 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. Conclusion Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted. J Clin Oncol 28:3167-3175. © 2010 by American Society of Clinical Oncology
2,669 citations