piperidines and Pleural-Effusion

Topics: Colitis, Ulcerative; Humans; Piperidines; Pleural Effusion; Pyrimidines

The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors.. Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial.. Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks.. Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase II as Topic; Creatinine; Diarrhea; Edema; Exons; Humans; Hypoalbuminemia; Lung Neoplasms; Mutation; Nausea; Piperidines; Pleural Effusion; Protein Kinase Inhibitors; Pyridazines; Pyrimidines; Vomiting

Chylothorax is an infrequent pleural effusion often caused by traumatic or nontraumatic injury to the thoracic duct. Nontraumatic chylothorax caused by chronic lymphocytic leukemia (CLL) is rarely reported. Previous experience has implied that the main factor affecting the treatment of chylothorax is whether the anti-cancer treatment is effective. The patient diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) before the hospital admission, and not received any treatment. After four months, he had progressive dyspnea. Chest computed tomography (CT) scan showed bilateral pleural effusion with progressive lymphadenopathy, and massive chylous pleural effusion was drained by closed thoracic drainage. After a course of chemotherapy including fludarabine, cyclophosphamide and rituximab (FCR), the patient developed agranulocytosis and his pleural effusion was still abundant. After careful consideration, the patient refused to receive following chemotherapy and chose to take ibrutinib orally. Two months after oral ibrutinib, ultrasound examination showed that pleural effusion completely disappeared. In the next one year, the patient had a routine follow-up and was in good condition. To our knowledge, this is the first report of ibrutinib in the treatment of chylothorax associated with CLL. Ibrutinib provides a more palliative treatment for elderly CLL patients with chylothorax.

Topics: Adenine; Aged; Chylothorax; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Pleural Effusion

Conventional therapies for patients with lung cancer have reached a therapeutic plateau. We therefore evaluated the feasibility of combined vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and epidermal growth factor (EGF) receptor (EGFR) targeting with radiation therapy in an orthotopic model that closely recapitulates the clinical presentation of human lung cancer.. Effects of irradiation and/or ZD6474, a small-molecule inhibitor of VEGFR2 and EGFR tyrosine kinases, were studied in vitro for human lung adenocarcinoma cells by using proliferation and clonogenic assays. The feasibility of combining ZD6474 with radiation therapy was then evaluated in an orthotopic model of human lung adenocarcinoma. Lung tumor burden and spread within the thorax were assessed, and tumor and adjacent tissues were analyzed by means of immunohistochemical staining for multiple parameters, including CD31, VEGF, VEGFR2, EGF, EGFR, matrix metalloproteinase-2 and -9, and basic fibroblast growth factor.. ZD6474 enhanced the radioresponse of NCI-H441 human lung adenocarcinoma cells by a factor of 1.37 and markedly inhibited sublethal damage repair. In vivo, the combined blockade of VEGFR2 and EGFR by ZD6474 blocked pleural effusion formation and angiogenesis and enhanced the antivascular and antitumor effects of radiation therapy in the orthotopic human lung cancer model and was superior to chemoradiotherapy.. When radiation therapy is combined with VEGFR2 and EGFR blockade, significant enhancement of antiangiogenic, antivascular, and antitumor effects are seen in an orthotopic model of lung cancer. These data provide support for clinical trials of biologically targeted and conventional therapies for human lung cancer.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Combined Modality Therapy; DNA Repair; Epidermal Growth Factor; ErbB Receptors; Feasibility Studies; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neovascularization, Pathologic; Piperidines; Pleural Effusion; Quinazolines; Radiation Tolerance; Radiation-Sensitizing Agents; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays

Topics: Anti-Allergic Agents; Collapse Therapy; Disease; Histamine H1 Antagonists; Piperidines; Pleura; Pleural Diseases; Pleural Effusion