Second-line therapy for non-small-cell lung cancer.

Carcinogenesis is a complex pathological process induced by abnormalities in the genome, cell-cycle dysregulation, loss of the programmed cell death process, and upregulation of oncogenic pathways associated with proliferation, migration, and survival, among others. Despite recent advances in molecular and tumor biology in non-small-cell lung cancer (NSCLC) and the introduction of several targeted agents, the disease continues to have a dismal survival. Nonetheless, the future looks promising; conventional cytotoxic chemotherapy regimens in combination with targeted agents have shown better response rates and survival than those seen in the past. These targeted agents have the advantage of blocking or inhibiting specific pathways necessary for tumor growth, proliferation, and metastases, without significantly affecting quality of life by having an acceptable toxicity profile. Thus, these novel agents harbor a hope in the treatment of NSCLC and many other malignant diseases when they can be used either in combination with other chemotherapy drugs in several lines of treatment or as a single agent in maintenance therapy until progression of disease, or even more attractively, in combination with other targeted agents themselves. In this review, we discuss second-line treatments for patients who have NSCLC, including targeted agents and their development in this specific setting as part of our armamentarium in lung cancer.

Gene expression profiling in breast cancer.

In recent years, molecular research has translated into remarkable changes of breast cancer diagnostics and therapeutics. Molecular tests such as the 21 gene expression test (Oncotype DX(TM)) and 70 gene microarray test (MammaPrint(®)) have revolutionized the predictive and prognostic tools in the clinic. By stratifying the risk of recurrence for patients, the tests are able to provide clinicians with more information on the treatment outcomes of using chemotherapy, HER2 targeted therapy or endocrine therapy or the combination of the therapies for patients with particular genetic expressions. However, it is still questionable for clinical applications as some areas remain unclear and that the true benefit still needs prospective evaluation. Such studies are under way and are anxiously awaited. In this paper, the limitation of the molecular tests are discussed. As we are moving towards personalized medicine, molecular profiling will not only result in better outcomes but in a certain proportion of patients, likely will spare unnecessary use of cytotoxic compounds and reduce the cost to the health care systems.

Safety and efficacy of pemetrexed in maintenance therapy of non-small cell lung cancer.

Lung cancer incidence continues to rise and is the number one cause of cancer death in both men and women worldwide with projected 221,130 new cases and 156,940 deaths in the United States in 2011.1 Non-small cell lung cancer (NSCLC) represents more than 85% of the cases with most patients having either locally advanced or metastatic disease at the time of initial diagnosis, and approximately 60%-70% of them have an adenocarcinoma histologic subtype. In the last three years, we have seen several advances in the management of NSCLC, with several factors playing an important role in the treatment decision making process. Maintenance therapy has been added to the algorithm of NSCLC management and Pemetrexed has been studied as single agent or in combination in this setting with recent studies showing safety and improved progression free survival (PFS) and/or overall survival (OS), still the disease for the most part has a dismal outcome. More research work needs to be done to identify which patients truly benefit from these approaches, and to whom we should offer maintenance or switch maintenance vs. close observation.

Emerging role of multikinase inhibitors for refractory thyroid cancer.

Thyroid cancer incidence continues to increase, remaining the most common endocrine malignancy. The need for effective systemic therapies combined with high incidence of driver mutations and overexpression of molecular pathways make refractory thyroid cancer an ideal candidate for treatment with novel agents. Multikinase inhibitors have caused a paradigm shift in the treatment of patients with advanced iodine-refractory thyroid cancer. These agents have shown to be the most effective systemic therapy for this disease not only causing prolonged responses but also improving survival. The activity of these agents inhibiting several pathways simultaneously, such as rearranged during transfection protooncogene, mitogen-activated protein kinase, and angiogenesis, can probably explain the effectiveness in controlling the progression of this malignancy. Several of these agents are currently on clinical studies in patients with differentiated and medullary thyroid cancer and most of them are showing promising clinical activity. With the approval of vandetanib for the treatment of medullary thyroid cancer, a new era in the management of this disease has begun. The molecular rationale for the use of these drugs for thyroid cancer is discussed as well as their promising clinical results.

Novel molecular targeted therapies for refractory thyroid cancer.

The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine-refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B-Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR-2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi-kinase inhibitors such as axitinib, sorafenib, motesanib, and XL-184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer.

Development of targeted therapy for squamous cell carcinomas of the head and neck.

Targeted therapy is a very exciting era in the treatment of squamous cell carcinomas of the head and neck. After adding cetuximab to conventional chemotherapy and radiation therapy, we are strongly considering the role of induction chemotherapy with the addition of docetaxel. At the same time, other new treatments, especially targeted agents and novel combined regimens, are being evaluated in ongoing clinical trials. For example, several trials are attempting to combine docetaxel and cetuximab in chemoradiation or induction settings. However, in the near future we are likely to see a strong presence of targeted agents that have been found to be not only effective, but also less toxic than conventional chemotherapeutic agents. Their toxicity profiles make them eligible for addition to radiation treatment strategies, as well as other chemotherapy agents, or even for replacing these chemotherapy agents. In this article, we are going to review the indications and current role of cetuximab, tyrosine kinase inhibitors (gefitinib and erlotinib), dual inhibitors, IGF receptor inhibitors, as well as other agents that are in development for treatment of head and neck squamous cell carcinomas.

Nasopharyngeal carcinoma: alternative treatment options after disease progression.

Nasopharyngeal carcinoma is a rare malignancy with an incidence well under one per 100,000 person-years, except for some geographic areas, such as Asia. The prognosis of nasopharyngeal carcinoma is related to its potential for locoregional invasion and metastatic spread. Radiotherapy alone remains the standard treatment for early stages. However, for locally advanced disease, chemotherapy may offer some benefit as a radiosensitizer while treating microscopic spread disease. Chemoradiotherapy is now the standard treatment for locally advanced and/or node-positive patients. Platinum-based therapy is the preferred regimen for this therapeutic approach. In this review, we discuss all treatment modalities available for nasopharyngeal carcinoma, including the standard of care and what therapeutic options could be available for those patients who progress after the standard treatment has been delivered.