Expert opinion on pharmacotherapy
-
Expert Opin Pharmacother · Dec 2016
ReviewCurrent and developing therapies for the treatment of non-small cell lung cancer with ALK abnormalities: update and perspectives for clinical practice.
The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1. Given that resistance occurs within approximately 12 months, in order to develop more potent inhibitors and to increase drug penetration to CNS, innovative ALK-inhibitors were developed. Second-generation ALK inhibitors Ceritinib (LDK378), Alectinib (CH5424802/RO5424802) and Brigatinib (AP26113) have shown significant clinical activity, and were rapidly approved by regulatory agencies. ⋯ Areas covered: In this review, the efficacy and tolerability of Crizotinib for 1st and 2nd-line treatment, and the clinical and preclinical data that led to the development of innovative second and third generation ALK-inhibitors are described. Expert opinion: The better characterization of the mechanisms of resistance to Crizotinib led to the development of newest drugs, which are active both after Crizotinib failure and in patients naïve from ALK-inhibitors. Tumor characterization at disease progression will allow to further personalize the treatment by establishing optimal sequences, which represent tough challenges for the future research in this field of cancer treatment.
-
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy. Areas covered:The preclinical development and scientific rationale, pharmacokinetics, and clinical efficacy and safety of cabozantinib for the treatment of advanced RCC are reviewed. ⋯ Expert opinion: Cabozantinib is the only therapy for advanced RCC that has improved PFS, ORR, and OS in a pivotal phase 3 trial after prior antiangiogenic therapy. While no clinical trials have been published comparing cabozantinib with another TKI, available clinical data suggest it could be the most efficacious TKI for second-line therapy. Preliminary encouraging results have also been reported in a phase 2 trial in untreated poor- and intermediate- risk patients with RCC, indicating that treatment with cabozantinib may also be beneficial in the first-line setting.
-
Fracture healing is a complex physiological process. As impaired fracture healing is more frequent in osteoporotic subjects, anti-osteoporotic drugs could have some impact on this process. ⋯ A PubMed/Medline search was undertaken combining the terms 'fracture healing', 'anti-resorptive drugs', 'anabolic agents', 'anti-osteoporotic drugs'. Expert opinion: As clinical evidence on the role of anti-osteoporotic drugs in the process of fracture healing consists mainly of case reports or studies with a relatively small number of patients, large randomized clinical trials are needed in order to extend to the human setting the promising results on these agents as inductors or co-adjuvants of bone healing derived from animal studies.
-
Expert Opin Pharmacother · Dec 2016
ReviewSufentanil sublingual tablet system for the management of postoperative pain.
Intravenous patient-controlled opioid analgesia has been an important improvement in addressing insufficient management of acute postoperative pain for over 40 years. However, there are number of weaknesses for intravenous patient-controlled analgesia, including operator and device error, intravenous line patency issues, and risk of catheter-related infection, all of which contribute to the complications and increase in cost of care. The sublingual sufentanil tablet system is a major evolution in both drug and technological management of postoperative pain. ⋯ Expert opinion: The sublingual sufentanil tablet system can decrease intravenous opioid based patient-controlled analgesia related complications and safety issues. Current clinical studies have demonstrated this noninvasive-novel system to be safe and effective in management of acute pain in the postsurgical setting. Researchers should focus on comparing it with other available patient controlled analgesia modalities and evaluating the efficiency and cost effectiveness of the sublingual sufentanil tablet system.
-
Expert Opin Pharmacother · Dec 2016
ReviewUpdate on pharmacotherapy for treatment of opioid use disorder.
Opioid Use Disorder (OUD) is a significant public health concern, negatively impacting the medical, psychological, and social domains of an individual's life as well as creating substantial burdens for society. Effective treatment interventions are necessary for reduction of OUD and its consequences. Pharmacotherapy represents a central component of management. ⋯ Expert opinion: Medication therapy for treatment of OUD has demonstrated efficacy and is of great clinical benefit. While agonist treatment with methadone or buprenorphine remains the gold standard, there is an important place for use of long-acting antagonist therapy with naltrexone. Continued investigation into treatment paradigms and behavioral platforms which optimize medication therapy is most needed.