Expert review of anticancer therapy
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Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA). Overall, niraparib is well tolerated and its toxicities, primarily hematologic, are manageable especially with recently released initial dose modification guidelines based on weight and baseline platelet count. The role of niraparib as maintenance following frontline platinum-based chemotherapy as well as in the treatment of recurrent high-grade serous ovarian cancer is an active area of investigation. ⋯ Expert commentary: Niraparib introduced the use of PARP inhibitors regardless of biomarker status. Recent studies highlight the critical need for more accurate biomarkers to identify patients most likely to benefit from treatment with PARP inhibitors. In the next 5 years, we anticipate further expansion of and elucidation regarding the optimal indication for use of niraparib in the treatment of ovarian cancer.
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Expert Rev Anticancer Ther · Jul 2018
ReviewChallenges and concerns of persistent opioid use in cancer patients.
As a result of advancements in the diagnosis and treatment of cancer, two-thirds of individuals suffering with cancer survive more than 5 years after diagnosis, resulting in a large proportion of patients with chronic cancer pain alone or associated with chronic noncancer pain. There is a paucity of literature in reference to diagnosis and management of chronic cancer pain, specifically in relation to persistent opioid use, its effectiveness, and adverse consequences. Areas covered: This review covers the prevalence of chronic cancer pain and its association with multiple comorbidities, persistent opioid use and related consequences, and challenges in managing persistent chronic cancer pain patients. ⋯ Expert commentary: Despite extensive availability of opioids and related common adverse consequences, including the potential for escalating use, abuse, and deaths, greater awareness is needed to counteract the present atmosphere and appropriately manage patients with chronic cancer pain. Chronic cancer pain is a complex biopsychosocial phenomenon with multiple comorbidities. Opioid therapy has become extremely complex with negative connotations related to escalating abuse and related deaths.
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Expert Rev Anticancer Ther · Jun 2018
ReviewCurrent approaches to challenging scenarios in myeloproliferative neoplasms.
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia and primary myelofibrosis are clonal hematological malignancies that originate at the level of the hematopoietic stem cell, and are characterized by excessive proliferation of cells belonging to one or more of the myeloid lineages. Central to the pathogenesis of the MPNs is constitutive activation of the JAK/STAT signaling pathway due to a family of driver mutations affecting JAK2, CALR or MPL. These disorders share common clinical and laboratory features, a significant burden of systemic symptoms, increased risk of developing arterial and venous thrombotic events, and the potential to progress to myelofibrosis and acute leukemia. ⋯ Our conclusions and recommendations are based on a literature search using MEDLINE and recent meeting abstracts using the keywords, focusing on publications directly addressing these scenarios and on recent contributions to the field. Expert commentary: Multi-center efforts to study large cohorts of MPN patients have led to more uniform and evidence-based approaches to key aspects in MPN management. However, treatment strategies to deal with specific clinical scenarios are lacking.
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Expert Rev Anticancer Ther · Jun 2018
Review Comparative StudyLenvatinib for the treatment of kidney cancer.
Sequential administration of single targeted agents has evolved as the dominant paradigm in advanced RCC treatment. Lenvatinib plus everolimus is the first combination therapy in advanced RCC to show improvement in efficacy compared to monotherapy in advanced RCC while maintaining manageable toxicity profile. Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus. ⋯ Expert commentary: Lenvatinib is a new VEGF receptor-targeted tyrosine kinase inhibitor approved in combination with everolimus for second-line therapy in patients with advanced renal cell carcinoma progressing on a first-line VEGF receptor-targeted tyrosine kinase inhibitor. The combination of lenvatinib with everolimus significantly improved progression-free survival compared with everolimus with a hazard ratio of 0.40 and increased objective response to 43%. Optimal sequence of therapy targeting the tumor and the immune system remains a challenge and further investigation is warranted.
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Expert Rev Anticancer Ther · May 2018
Review Comparative StudyNivolumab in squamous cell carcinoma of the head and neck.
The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. ⋯ Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.