Expert review of clinical pharmacology
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The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. ⋯ Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that exerts its anti-tumor effect through blocking the interaction of the immune inhibitory molecule PD-1 with its ligands. Its effect has been most convincingly demonstrated in the setting of advanced melanoma, with growing evidence of clinical responses across a broad spectrum of other solid and hematological malignancies.
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Expert Rev Clin Pharmacol · Jan 2015
ReviewAfamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria.
The application of afamelanotide, an α-melanocyte stimulating hormone agonistic analogue to protoporphyria, a disease with absolute sunlight-intolerance is discussed. The clinics, genetics and existing therapies of protoporphyria are described. The physiological receptor-mediated intracellular signaling of α-melanocyte stimulating hormone and effects of receptor variants are outlined. ⋯ The trial results were significant, although the effects were not very large in absolute terms, and the risk-safety profile is favorable today. Based on the high compliance rate and the excellent consistency in clinical effectiveness during six years of compassionate use program in Switzerland, we expect afamelanotide and analogues to become a prospective therapeutic tool. Moreover, we hope that dosage forms suitable for children will be developed in future, as children and adolescents suffer most in protoporphyria.
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Expert Rev Clin Pharmacol · Jan 2015
ReviewUsing real-world healthcare data for pharmacovigilance signal detection - the experience of the EU-ADR project.
A prospective pharmacovigilance signal detection study, comparing the real-world healthcare data (EU-ADR) and two spontaneous reporting system (SRS) databases, US FDA's Adverse Event Reporting System and WHO's Vigibase is reported. The study compared drug safety signals found in the EU-ADR and SRS databases. ⋯ The EU-ADR system may have a greater potential for detecting signals for events occurring at higher frequency in general population and those that are commonly not considered as potentially a drug-induced event. Factors influencing various differences between the datasets are discussed along with potential limitations and applications to pharmacovigilance practice.
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Expert Rev Clin Pharmacol · Jan 2015
ReviewFentanyl buccal tablet for the treatment of cancer-related breakthrough pain.
Fentanyl buccal tablet (FBT) (FENTORA) is indicated for the management of breakthrough pain (BTP) in patients with cancer pain and who are tolerant to ≥60 mg of oral morphine equivalents, at least with the current availability of the minimal strength of 100 μg. FBT uses the OraVescent technology to further increase the rate and extent of absorption of fentanyl. ⋯ It has been recommended that administration should be tailored to the patient's individual requirement, through dose titration starting from the lowest dose to find the effective dose. However, recent studies have demonstrated that predictable doses calculated from the basal opioid regimen are safe and more effective than doses achieved after dose titration.
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Expert Rev Clin Pharmacol · Jan 2015
ReviewDabrafenib in combination with trametinib for the treatment of metastatic melanoma.
Oncogenic BRAF mutations are present in approximately 40-50% of patients with metastatic melanoma. Targeting BRAF mutations with either small molecule inhibitors of BRAF or one of the downstream mediators of oncogenic BRAF - MEK - is associated with improved outcomes compared with chemotherapy and has led to the US FDA approval of two BRAF inhibitors - vemurafenib and dabrafenib - and the MEK inhibitor trametinib. Further, the combination of dabrafenib and trametinib is well tolerated and associated with higher responses and improved survival compared with single-agent BRAF inhibitors.