Annals of oncology : official journal of the European Society for Medical Oncology
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Cancer incidence will increase as the population ages; there will be a 50% increase in new cancer cases over the next 20 years, and the biggest rates of increase will occur in the developing world. Owing to technical advances in the care of critical illness, as it is the case in elderly people with advanced cancer, physicians, patients and families are often confronted with ambiguous circumstances in which medical advances may inadvertently prolong suffering and the dying process rather than bring healing and recovery. In this review of the ethical issues confronting physicians who care for patients with advanced life-limiting illnesses like cancer, a philosophical debate continues in the medical community regarding the rightness or wrongness of certain actions (e.g. physician-assisted death, euthanasia), while at the same time there is a strong desire to find a common ground for moral discourse that could guide medical decision-making in this difficult period in the lives of our patients. ⋯ Spiritual issues often come to the fore. An interdisciplinary healthcare team can help in these areas. The goals of this review are to raise the awareness of doctors, nurses and other members of the healthcare team to the important ethical issues that must be addressed in providing medical care to elderly patients with advanced cancer; and also to encourage members of the healthcare team to take the ethical issues seriously so that we can improve the circumstances of a vulnerable group of patients-the elderly patients with cancer.
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Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. A well-defined precursor lesion (adenoma) and a long preclinical course make CRC a candidate for screening. This paper reviews the current evidence for the most important tests that are widely used or under development for population-based screening. ⋯ FS screening reduces CRC incidence and CRC mortality by removal of adenomas; FOBT reduces CRC mortality by early detection of cancer. Several other tests are available, but none has been evaluated in randomised trials. Screening strategies differ considerably across countries.
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Non-inferiority clinical trials (NIFCTs) aim to demonstrate that the experimental therapy has advantages over the standard of care, with acceptable loss of efficacy. We evaluated the purposes underlying the selection of a non-inferiority design in oncology and the size of their non-inferiority margins (NIFm's). ⋯ Cancer NIFCT harbor serious methodological and ethical issues. Many use large NIFm and nearly one-fifth did not state a clear purpose for selecting a non-inferiority design.
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Approximately 15%-23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed. ⋯ Non-HER2-targeted therapy is a promising means of overcoming resistance to HER2-targeted treatment. Ongoing clinical studies will provide additional information on the efficacy and safety of novel targeted therapies in HER2-resistant advanced breast cancer.
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In 2011, two therapies were approved for the treatment of metastatic melanoma: ipilimumab, an immunotherapeutic agent, and vemurafenib, a BRAF kinase inhibitor. These approvals were based on data from phase III trials, which showed that treatment with these agents produced substantial improvements in overall survival (OS). Ipilimumab has been investigated in two phase III trials: one as monotherapy in patients with pretreated metastatic melanoma at a dose of 3 mg/kg and the second in combination with dacarbazine (DTIC) chemotherapy in patients with previously untreated metastatic melanoma at a dose of 10 mg/kg. ⋯ Established guidelines can be used to manage the majority of irAEs effectively. Proposed modifications made to the existing response criteria mean that the clinician can accurately detect immune-related responses that would have been considered representative of progressive disease using conventional criteria. Further research is warranted to establish how immunotherapeutic agents can be combined with conventional agents, with each other or with molecularly targeted agents such as vemurafenib, to further optimise clinical outcomes.