Few standard second-line treatment options exist for advanced sarcoma patients. Some of these patients are offered early-phase clinical trials involving targeted or nontargeted agents. This review outlines recent phase 1 trials involving sarcoma patients, explores current challenges and highlights future opportunities in sarcoma developmental therapeutics. RECENT FINDINGS: New molecularly targeted phase 1 studies have demonstrated efficacy in sarcomas. For instance, insulin-like growth factor-1 receptor (IGF1R) antibodies have produced single agent activity in Ewing's sarcoma. Other promising novel agents include an agonist for the apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) for chondrosarcoma, small molecule inhibitor crizotinib for anaplastic lymphoma kinase (ALK)-rearranged inflammatory myofibroblastic tumor, cedarinib for alveolar soft part sarcoma, and rexin-G, a tumor targeted retrovector for osteosarcoma. In addition, different combinations of chemotherapy in combination with newer agents such as trabectedin exhibited efficacy in advanced soft tissue sarcoma. SUMMARY: Patients with refractory sarcoma demonstrate benefit from treatment with targeted drugs even in the setting of phase 1 trials. Sarcomas that have a defined translocation and those that express specific activated kinases are particularly promising tumors for targeted therapy. The primary challenge is identifying the biomarkers predictive of response or resistance, matching them with specific patient histology, resulting in successful translation of biology into clinical benefit.

• MeSH
• cílená molekulární terapie MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• klinické zkoušky, fáze I jako téma MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádory kostí farmakoterapie   MeSH
• prognóza MeSH
• protinádorové látky terapeutické užití   MeSH
• sarkom farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Experiments on dogs were performed to investigate the efficacy of various defibrillation impulse waveforms. The results showed that the decisive factors for the effectiveness of the defibrillation impulse of certain shape are its relationship to the carciac tissue accomodation and the duration of the suprathreshold current flow. For cardiac defibrillation the most convenient impulse is therefore the impulse with the highest rate of rise of the leading edge as well as the trailing edge. The amplitude of the rear trailing edge of the defibrillation impulse should be either equal or higher than the amplitude of the front leading edge. That means that rectangular or trapezoidal impulses with an ascending slope may be most conveniently used for cardiac defibrillation. The biologically optimal duration of the trapezoidal impulse with an ascending slope proved to range from 7 to 14 msec. The authors emphasize the inevitability of additional characteristics of the defibrillation impulse by its peak current and total energy contents.

• MeSH
• elektrická defibrilace metody   MeSH
• elektrická stimulace MeSH
• psi MeSH
• srdce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH