Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Jan 2016
ReviewOvercoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib.
In up to 5% of non-small cell lung cancer (NSCLC) patients, the EML4-ALK translocation drives tumor progression. Treatment with the ALK inhibitor crizotinib is more effective than standard chemotherapy. However, resistance to crizotinib occurs after approximately 8 months. ⋯ Cells with ALK expression are more sensitive to ceritinib than crizotinib (IC50 25 nM vs. 150 nM, respectively). Alternative second-generation ALK inhibitors such as Alectinib, Brigatinib and PF-06463922 are currently in development, each affecting different crizotinib-resistant ALK target mutations. Genetic identification of crizotinib-resistant mutants is essential for selecting the optimal treatment strategy in NSCLC patients to overcome resistance and to increase progression-free survival.
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Expert Rev Anticancer Ther · Jan 2016
ReviewEmerging targeted therapies in non-small cell lung cancer.
Lung cancer is the leading cause of cancer-related deaths in United States, accounting for more than one-fourth of the deaths annually. Although comparatively rare and relatively less studied, genetic abnormalities other than epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and Kirsten rat sarcoma (KRAS) mutations account for significant proportion of the driver mutations identified thus far. ⋯ Recruiting patients with these rarer mutations to well-designed, large multicenter trials to further validate the use of targeted agents remains a challenge. The clinical data and ongoing trials with these agents are reviewed in this article.
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Expert Rev Anticancer Ther · Jan 2016
ReviewDose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia.
Gemtuzumab ozogamicin, an anti-tumour antibiotic linked to an anti-CD33 antibody (Mylotarg®), has been well studied in AML in adults but to a lesser extent in children. No review has yet been published on the dose-related toxicity and efficacy of gemtuzumab ozogamicin in pediatric AML patients. Here we looked at 14 studies then scatterplots and linear regressions were used to estimate the relationship between the dose of gemtuzumab and its toxicity and efficacy. ⋯ Data indicate that higher doses of gemtuzumab ozogamicin account for more adverse events. The data do not show that a high dose is required for anti-leukemic efficacy of gemtuzumab ozogamicin. This study also indicates that there seems to be a role for gemtuzumab ozogamicin in the treatment of pediatric AML and further studies are required to assess its optimal dose, schedule and balance between efficacy and side-effects.
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Expert Rev Anticancer Ther · Jan 2016
ReviewNivolumab for the treatment of classical Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab.
Cancer cells are able to escape surveillance from the immune system by co-opting physiologic mechanisms such as the programmed cell death-1 (PD-1) receptor pathway. Agents able to block the interaction between the PD-1 receptor and its ligands have the potential to release T cells from tumor-induced suppression and eradicate malignant cells. ⋯ This agent has been tested in patients with advanced Hodgkin lymphoma (HL) and showed impressive results in a phase I trial. Here we review the profile of Nivolumab including its pharmacological properties, clinical efficacy and safety in patients with advanced classical HL.
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Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. Here we address the issue of maintenance therapy as part of a therapeutic approach of multiple myeloma patients focusing on the potential role of ixazomib.