Targeted treatment of non-small cell lung cancer

Non-small cell lung cancer (NSCLC) has made a remarkable development in recent decades with respect to its perception. In the late 1990s it was the problem child as the main cause of cancer with increasing tendencies, especially in women and with a pronounced stigmatization. It is now the role model as a biologically rational targeted treatment based on molecular dependencies of the tumor with a vast improvement of the traditionally poor survival times. Molecular tumor boards have long followed the NSCLC example in the assessment of targeted treatment approaches for other tumor entities. This review article gives an overview of the current possibilities for targeted treatment of NSCLC, which nowadays are applicable for nearly one third of all patients with NSCLC

Efficiency of B-RAF-/MEK-inhibitors in B-RAF mutated Ameloblastoma: Case report and review of literature

Background: Ameloblastoma is a benign but locally invasive and aggressive odontogenic tumor harboring activating BRAF V600E mutations in about two thirds of the cases. Case presentation: Neoadjuvant therapy with Dabrafenib and Trametinib was given to a 42-year-old male patient with recurrent ameloblastoma of the right mandible with a BRAF V600E mutation for 18 months. The patient manifested an excellent response to the therapy with remarkable reduction in tumor size from 72.6 mm to 55.9 mm. Histopathologically, the tumor underwent significant degenerative changes with only a few sparse vital residuals revealing 0 % Ki67 proliferative index. Conclusions: Neoadjuvant therapy with BRAF-inhibitors or BRAF-MEK-inhibitors is an effective means to reduce the size of mandibulary ameloblastomas. We propose the consideration of neoadjuvant therapy in future treatment modalities to minimize post-surgical morbidity and facial deformations

A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients

Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE). We present a modeling and simulation framework for the most common erlotinib-induced AE, rash, and diarrhea, providing insights into erlotinib toxicity. We used the framework to investigate the safety of high-dose erlotinib pulses proposed to limit acquired resistance while treating NSCLC. Continuous-time Markov models were developed using rash and diarrhea AE data from 39 NSCLC patients treated with erlotinib (150 mg/day). Exposure and different covariates were investigated as predictors of variability. Rash was also tested as a survival predictor. Models developed were used in a simulation analysis to compare the toxicities of different regimens, including the previously mentioned pulsed strategy. Probabilities of experiencing rash or diarrhea were found to be highest early during treatment. Rash, but not diarrhea, was positively correlated with erlotinib exposure. In contrast with some common understandings, radiotherapy decreased transitioning to higher rash grades by 81% (p<0.01), and experiencing rash was not correlated with positive survival outcomes. Model simulations predicted that the proposed pulsed regimen (1600 mg/week+50 mg/day remaining week days) results in a maximum of 20% of the patients suffering from severe rash throughout the treatment course in comparison to 12% when treated with standard dosing (150 mg/day). In conclusion, the framework demonstrated that radiotherapy attenuates erlotinib-induced rash, providing an opportunity to use radiotherapy and erlotinib together, and demonstrated the tolerability of high-dose pulses intended to address acquired resistance to erlotinib

Monitoring reversible and irreversible EGFR inhibition with erlotinib and afatinib in a patient with EGFR-mutated non-small cell lung cancer (NSCLC) using sequential [ 18F]fluorothymidine (FLT-)PET

© 2012 Elsevier Ireland Ltd. All rights reserved