Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85% of all new lung cancer diagnosis. The majority of people with NSCLC are unsuitable for surgery since most patients have metastatic disease at diagnosis. About 60% of brain metastases arise from lung cancer. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery, chemotherapy and new biologic agents. Angiogenesis is essential for the development and progression of cancer, and vascular endothelial growth factor (VEGF) is a critical mediator of tumour angiogenesis. One of the targeted approaches most widely studied in the treatment of NSCLC is the inhibition of angiogenesis. Bevacizumab, an anti-VEGF recombinant humanized monoclonal antibody, is the first targeted agent which, when combined with chemotherapy, has shown superior efficacy versus chemotherapy alone as first-line treatment of advanced non-squamous NSCLC patients. Patients with central nervous system (CNS) metastases have initially been excluded from bevacizumab trials for the risk of cerebral haemorrhage as a result of the treatment. Nevertheless, the available data suggest an equal risk of intracranial bleeding in patients with CNS metastases treated with or without bevacizumab therapy. Several other anti-angiogenetic drugs are being investigated in the treatment of advanced NSCLC patients, but results of their activity specifically in CNS metastases are still lacking. This review will focus on the potential role of bevacizumab and other anti-angiogenetic agents in the treatment of brain metastases from NSCLC.
Breast cancer arises in about 48% of patients older than 65 years and more than 30% occurs in those over 70 years being the leading cause of cancer-related death in women older than 65. Elderly patients tolerate chemotherapy poorly compared to their younger counterpart because of progressive reduction of organ function and comorbidities related to age. For this reason, the elderly have been excluded from or underrepresented in most cancer studies and, in clinical practice, they often receive inadequate and untested treatments. For adjuvant chemotherapy, a low percentage of patients over 70 years of age were included in few trials and always in a proportion much lower than the prevalence of cancer in that age group. Adjuvant chemotherapy, preferably including an anthracycline especially in patients with HER-2/neu-positive tumours, seems to be beneficial in older women who have substantial risk of dying of breast cancer. To date even if there is no specifically randomised study, single-agent chemotherapy probably might be considered a reasonable treatment for advanced breast cancer in the elderly. One of the actual main field of clinical research in the treatment of breast cancer is the role of targeted therapies. Chronologic age is a risk factor for toxicities such as myelosuppression and mucositis, and older patients may require more supportive care. In order to plan medical treatment in breast cancer elderly patients is mandatory to practice a comprehensive geriatric assessment that includes evaluation of comorbidities, functional dependence, socio-economic, emotional and cognitive conditions, an estimate of life expectancy and recognition of frailty. The authors review the literature regarding age-specific chemotherapeutic issues in the management of breast cancer elderly patients.
Erlotinib may be effective in patients with non-small cell lung cancer who were previously and successfully treated with gefitinib. However, careful selection of these patients is needed.
Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed over the age of 65 and approximately one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly as compared to their younger counterparts, because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy, the standard medical treatment of advanced NSCLC. At present, for early stages of the disease there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems to determine no survival advantage as compared to the radiation therapy alone. In advanced disease, single agent vinorelbine has proven to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps even the quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The two main research-lines to be explored in the near future are the introduction of biological agents in the treatment schemes and the development of specifically designed schedules of cisplatin-based regimens. However, practicing a multidimensional geriatric awsessment for individualized treatment choice in NSCLC elderly patients is mandatory.
More than 50% of lung cancer cases are diagnosed in patients over the age of 65 years, and about 30% are diagnosed in patients over the age of 70 years. Elderly patients do not tolerate chemotherapy as well as their younger counterparts, mainly because of the higher prevalence of comorbid conditions and organ failure in the elderly. Alternatives to conventional chemotherapy, such as new molecular targeted therapies, are of interest. This review summarizes current approaches and recent advances in the treatment of elderly patients with non-small cell lung cancer and gives a perspective on the future of molecular targeted therapies in this population. Epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors are discussed here, being, in our opinion, among the best candidates for clinical development in this setting. Their potential advantages in elderly patients include better tolerability than conventional chemotherapy.
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