Future oncology
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The PulMiCC trial is a randomized controlled trial testing the effect on survival of pulmonary metastasectomy in patients with colorectal cancer. In stage 1 of the trial patients with treated primary colorectal cancer metastatic to the lungs are invited to consent for protocol-based evaluation of their suitability for metastasectomy. ⋯ If there is uncertainty the patient is invited to consent to have the treatment arm assigned by randomization in stage 2 of PulMiCC. More than 300 patients have entered stage 1 and more than 70 are in stage 2.
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Review
Current and future targeted therapies for non-small-cell lung cancers with aberrant EGF receptors.
Expression of the EGF receptors (EGFRs) is abnormally high in many types of cancer, including 25% of lung cancers. Successful treatments target mutations in the EGFR tyrosine kinase domain with EGFR tyrosine kinase inhibitors (TKIs). ⋯ Because of the development of resistance to treatment of TKIs, there is a need to collect genomic information about EGFR levels in non-small-cell lung cancer patients. Herein, we focus on current molecular targets that have therapies available as well as other targets for which therapies will be available in the near future.
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Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. ⋯ Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
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Review
Optimizing the use of trabectedin for advanced soft tissue sarcoma in daily clinical practice.
Compared with conventional chemotherapy for advanced soft tissue sarcoma, trabectedin has several distinguishing characteristics which, when optimized, may maximize clinical benefits for patients. In this review, evidence is examined with the aim of answering some vital questions about the use of trabectedin in clinical practice. Who should be treated? When should patients be treated? For how long should patients be treated? What is the safety profile of trabectedin? How should trabectedin be administered? In brief, trabectedin has shown activity and clinical benefit in nearly all subtypes of soft tissue sarcoma. ⋯ Trabectedin has a role for treatment of elderly patients in whom alternatives are lacking, and can be administered for prolonged periods without cumulative toxicity. A statistically significant improvement in median progression-free survival has been observed when trabectedin is administered uninterrupted until disease progression. The flexibility of trabectedin administration in terms of dose, interval and duration allows for patient-tailored treatment optimization.
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ABSTRACT Rearrangement of ALK gene has been identified as exerting a potent transforming effect as driver oncogene in patients with non-small-cell lung cancer (NSCLC). Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases. ⋯ Resistance mechanisms such as secondary gatekeeper mutations in ALK gene and activation of other oncogenes have been identified to confer acquired resistance to crizotinib. This article reviews the pharmacological properties of crizotinib, preclinical and clinical results that led to its approval in ALK-positive NSCLC and current directions of clinical research in overcoming crizotinib resistance.