143 research outputs found
Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma
No full textLung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases
Erlotinib therapy in advanced non small-cell lung cancer
Full text linkErlotynib jest jednym z inhibitorów kinazy tyrozynowej receptora naskórkowego czynnika wzrostu. Terapia tymi cząsteczkami może przynieść korzyść taką jak wydłużenie czasu przeżycia oraz poprawy jakości życia w wyselekcjonowanej grupie chorych z niedrobnokomórkowym rakiem płuca (NDRP). Chorzy odnoszący największą korzyść z tej terapii to pacjenci z potwierdzoną obecnością mutacji aktywującej w obrębie genu EGFR, w dobrym stanie ogólnym. Leki te są dobrze tolerowane, podanie ich nie wymaga hospitalizacji co jest bardzo ważne dla chorych oraz ich rodzin. W pracy przedstawiono przypadek mężczyzny leczonego erlotynibem.Erlotinib is one of epithelial growth factor receptor tyrosine kinase inhibitors. Treatment of selected patient groups may result in prolonged survival time and improved quality of life during therapy. Patients who benefit most from this therapy are those with confirmed activating mutations within the EGFR gene, in good general condition. These drugs are well tolerated and do not require hospitalization, which is very important for the patients and their families We present the case of a male with advanced non small cell lung cancer who receives erlotinib
Leczenie ukierunkowane molekularnie chorych na niedrobnokomórkowego raka płuca
Full text linkRak płuca stanowi najczęstszą przyczynę zgonów z powodu choroby nowotworowej zarówno u mężczyzn, jak i u kobiet w Polsce i na świecie. Chorzy z rozpoznaniem niedrobnokomórkowego (NDRP) niepłaskonabłonkowego raka płuca, a także chorzy z nowotworem o nieokreślonym podtypie histologicznym (NOS) mogą odnieść korzyść z leczenia celowanego, ponieważ w tych typach nowotworów najczęściej stwierdza się obecność zaburzeń molekularnych, takich jak mutacja aktywująca w genie EGFR, rearanżacja genów ALK, ROS1 czy NTRK oraz mutacja w genie BRAF. Zaburzenia te są dodatnim czynnikiem predykcyjnym odpowiedzi na leczenie inhibitorami kinazy tyrozynowej. Podkreśla się konieczność oznaczeń molekularnych u chorych na zaawansowanego niedrobnokomórkowego niepłaskonabłonkowego raka płuca przed kwalifikacją do chemioterapii systemowej i w przypadku stwierdzenia zaburzeń molekularnych — zastosowania terapii celowanej w 1. linii leczenia
Leczenie ukierunkowane molekularnie chorych na niedrobnokomórkowego raka płuca
No full textRak płuca stanowi najczęstszą przyczynę zgonów z powodu choroby nowotworowej zarówno u mężczyzn, jak i u kobiet w Polsce i na świecie. Chorzy z rozpoznaniem niedrobnokomórkowego (NDRP) niepłaskonabłonkowego raka płuca, a także chorzy z nowotworem o nieokreślonym podtypie histologicznym (NOS) mogą odnieść korzyść z leczenia celowanego, ponieważ w tych typach nowotworów najczęściej stwierdza się obecność zaburzeń molekularnych, takich jak mutacja aktywująca w genie EGFR, rearanżacja genów ALK, ROS1 czy NTRK oraz mutacja w genie BRAF. Zaburzenia te są dodatnim czynnikiem predykcyjnym odpowiedzi na leczenie inhibitorami kinazy tyrozynowej. Podkreśla się konieczność oznaczeń molekularnych u chorych na zaawansowanego niedrobnokomórkowego niepłaskonabłonkowego raka płuca przed kwalifikacją do chemioterapii systemowej i w przypadku stwierdzenia zaburzeń molekularnych — zastosowania terapii celowanej w 1. linii leczenia
Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions
No full textLung cancer is the most common cause of cancer-related death worldwide, and the prognosis for stage IV remains poor. The presence of genetic alterations in tumor cells, such as EGFR and BRAF gene mutations, as well as ALK and ROS1 gene rearrangements, are indications for targeted therapies. Many such treatments are already registered and used on a wide scale. In comparison to standard chemotherapy, they can prolong not only progression-free survival but also overall survival. Moreover, they are able to provide excellent quality of life and rapid improvement of cancer-related symptoms such as dyspnea, cough and pain. Recent years have witnessed great advances in both molecular diagnostics and new molecular therapies for non-small-cell lung cancer. This review presents new therapeutic targets in NSCLC, as well as drugs of which the activity against NTRK, RET, MET or HER2 gene alterations (including EGFR exon 20 insertions) has either been confirmed or is currently being evaluated. Although these particular genetic alterations in NSCLC are generally rare, each accounting for 1–2% of patients, in total about half of all patients have molecular alterations and may ultimately receive targeted therapies
Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series
Full text linkBiliary tract cancer; Brigimadlin; EzabenlimabCàncer de les vies biliars; Brigimadlin; EzabenlimabCáncer de las vías biliares; Brigimadlina; EzabenlimabBackground: In patients with advanced biliary tract cancer (BTC), first-line chemotherapy plus immunotherapy has improved outcomes; however, second-line options that reflect the disease’s molecular heterogeneity are still needed. One emerging target is MDM2, amplified in ~5– 8% of BTC cases.
Methods: This is a subset analysis of two ongoing Phase Ia/Ib trials assessing patients treated with brigimadlin (BI 907828; a highly potent, oral MDM2–p53 antagonist) ± ezabenlimab (PD-1 inhibitor) ± BI 754111 (anti-LAG-3; n = 1).
Results: Results from 12 patients with BTC are shown (monotherapy: n = 6/combination: n = 6). Six patients achieved partial response (monotherapy: n = 2/combination: n = 4), four had stable disease; responses were durable. Brigimadlin had a manageable safety profile. Seven patients had dose reductions due to adverse events, but no treatment-related adverse events led to treatment discontinuation.
Conclusion: Brigimadlin demonstrated anti-tumor activity in patients with advanced MDM2-amplified BTC, and warrants further investigation
Epidemiological Situation Concerning Lung Cancer in Wielkopolska in 1975–2002
No full textLung cancer is the main cause of cancer deaths around the world. At 12% of all cancer incidents, lung cancer is the most frequent single cause of death, of both males and females. In 2002 among male population in Poland, lung cancer was the second, following heart failure, cause of death, ranging at 8% of deaths in general. It was third cause of death among females ranging at 2.3% in general. Considering cancer deaths in 2002 in Wielkopolska, lung cancer was most frequent cause of death among males (30%) and second frequent among females (10.4%). The last 25 years the number of deaths decreased among younger generation of males (first in the age group 20–44, later in the middle age group) and this phenomenon has dominated the general picture of cancer among males. However the increase of mortality rates in the older age group might be still observed. The constant increase of mortality has been observed among females, especially in the middle age group (45–64). It should be highlighted that the level of mortality has been equalled in both genders in the youngest age group (20–44), which means suddenly growing risk among young population of women in Wielkopolska
PD-1 Blockade in Anaplastic Thyroid Carcinoma
Full text linkCarcinoma anaplàsic de tiroides; Spartalizumab; Tumors sòlids metastàticsAnaplastic Thyroid Carcinoma; Spartalizumab; Metastatic solid tumorsCarcinoma anaplásico de tiroides; Spartalizumab; Tumores sólidos metastásicosPURPOSE
Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with BRAF-wild type disease. As part of a phase I/II study in patients with advanced/metastatic solid tumors, patients with anaplastic thyroid carcinoma were treated with spartalizumab, a humanized monoclonal antibody against the programmed death-1 (PD-1) receptor.
METHODS
We enrolled patients with locally advanced and/or metastatic anaplastic thyroid carcinoma in a phase II cohort of the study. Patients received 400 mg spartalizumab intravenously, once every 4 weeks. The overall response rate was determined according to RECIST v1.1.
RESULTS
Forty-two patients were enrolled. Adverse events were consistent with those previously observed with PD-1 blockade. Most common treatment-related adverse events were diarrhea (12%), pruritus (12%), fatigue (7%), and pyrexia (7%). The overall response rate was 19%, including three patients with a complete response and five with a partial response. Most patients had baseline tumor biopsies positive for PD-L1 expression (n = 28/40 evaluable), and response rates were higher in PD-L1–positive (8/28; 29%) versus PD-L1–negative (0/12; 0%) patients. The highest rate of response was observed in the subset of patients with PD-L1 ≥ 50% (6/17; 35%). Responses were seen in both BRAF-nonmutant and BRAF-mutant patients and were durable, with a 1-year survival of 52.1% in the PD-L1–positive population.
CONCLUSION
To our knowledge, this is the first clinical trial to show responsiveness of anaplastic thyroid carcinoma to PD-1 blockade
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