Search

SUMMARY We know how important antiangiogenesis therapy can be in cancer treatment. However, it took some time before the first compound became approved. Currently, several agents are approved and used against cancer. Moreover, the possible number of clinical indications and agents that are in development is extraordinary. A lot of questions regarding angiogenesis in cancer still remain unanswered. One of the major weaknesses is the fact that most of the approved agents do not have a predictive or prognostic biomarker that can be used to tailor these novel agents in terms of inducing the best possible antitumor effect. Many of these new targeted agents inhibit several tumorigenesis pathways, but most of the time only one of these pathways is the main driver for cancer proliferation. In this article, we present the most current clinical information available in antiangiogenic therapy and the potential development in non-small-cell lung cancer.

Colorectal cancer (CRC) was the third leading cause of cancer deaths in the United States in 2012, and most patients eventually develop metastatic disease. The use of cytotoxic chemotherapy, the antiangiogenesis drug bevacizumab, and the anti-EGFR monoclonal antibodies cetuximab and panitumumab have led to an improvement in median OS for metastatic CRC. Despite this improvement in survival, few agents have activity against CRC. Between 2006 and 2012, the FDA approved no new agents for patients with metastatic CRC (mCRC). Recently, the FDA has approved aflibercept and regorafenib for use in the treatment of patients with mCRC, and several new agents are currently in development. This paper reviews the use of new agents and new uses for established agents in mCRC.

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.

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.

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.

Many advances in the treatment of squamous cell carcinoma of the head and neck have occurred in the past few years. Since the advent of cetuximab, a chimeric monoclonal antibody against epidermal growth factor receptor, the search for other efficacious targeted therapies has awakened the interest and curiosity of researchers and clinicians. Initially, cetuximab demonstrated effectiveness as single agent in heavily pretreated patients diagnosed with head and neck cancer, and has demonstrated to improve locoregional control and survival when combined with radiotherapy. Thesuccess of cetuximab has transitioned to other settings and with different modalities such as in combination with other conventional cytotoxic agents in the metastatic setting, combined with radiation therapy as part of concurrent treatment, and lately, in combination with other agents in the induction phase of the sequential approach. In this review, we discuss all different modalities in combination with cetuximab and how cetuximab has been incorporated into other clinical settings with only one goal in mind: improve the survival rates of our patients.

There has not been a more exciting time in lung pathology than now. Because of new developments in tumor biology research and molecular pathology, the entire treatment algorithm of non small cell lung cancer has completely changed. Not too long ago, we still considered “carcinoma compatible with non small cell lung cancer” as a valid histopathologic diagnosis, good enough to start a patient on chemotherapy. Advances in pathology such as immunohistochemistry, gene expression profile, and the implementation of laboratory techniques like polymerase chain reaction, fluorescent in situ hybridization, and others have moved forward this field not only to identify a more accurate classification of this disease but also to identify new tumorigenesis pathways or active mutations which could serve as biomarkers with predictive and/or prognostic power to tailor our therapeutic agents. The fact that pathologists can accurately determine tumor histology as an adenocarcinoma or squamous cell carcinoma has a tremendous impact in the treatment selection. To date, the histologic subtype of non small cell lung cancer is the first step in customization of lung cancer therapy allowing us to choose among several chemotherapeutic agents. However, tumor biology has shown to be a stronger tool to personalized medicine, and pathology plays a crucial role in developing and improving these novel techniques. In this article, we will review the well established and most promising gene abnormalities as well as upregulated pathways recently found in lung cancer patients with the goal to use them to better classify these tumors and to identify new treatments for this disease.

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.

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.

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.

EXTRA RENAL METABOLIC ALKALOSIS: A TEACHING POINT: A CASE SERIES OF METABOLIC ALKALOSIS FROM CRACK COCAINE USE IN DIALYSIS PATIENTS Belisario Arango, Celine Rivera, Courtney Rowling, Jerry Yee Rakesh Lattupalli .Henry Ford Hospital, Detroit, MI-USA. Advanced renal disease is usually associated with metabolic acidosis. Metabolic alkalosis in a dialysis patient if not associated with vomiting is usually exogenous. We report case series of 4 patients admitted with metabolic alkalosis despite missing maintenance hemodialysis attributable to cocaine use. Purpose of the study is to delineate the possible underlying physiologic process for metabolic alkalosis in dialysis patients abusing cocaine. Methods: Data was collected from chart review of patients with ESRD presenting to the emergency department with history of missing dialysis and crack cocaine use from November 2008 to January 2009. Case series of 4 such patients with brief relevant clinical and laboratory data is presented here. Case ESRD HCO3 Urine Toxicology Last dialysis K BP Volume Status 1 Yes 27 Cocaine Positive 3 days ago 6.3 230/125 Volume overloaded 2 Yes 28 Cocaine Positive 4 days ago 5.3 153/105 Volume overloaded 3 Yes 26 Cocaine use reported 4 days ago 6.9 62/41 Not documented 4 Yes 34 Cocaine use reported 2 days ago 5.2 167/70 Volume overloaded

Abstract 3133 Introduction: Significant tonsil uptake is sometimes observed in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) after treatment. Some patients undergo tonsillectomy or FNA (fine needle aspiration) to rule out malignant involvement particularly when management depends on restaging (Figure 1). Our study describes the incidence and degree of tonsil FDG uptake in a large group of lymphoma patients that underwent PET scanning. Patients and Methods: Single institution, retrospective chart review by ICD code, 617 lymphoma patients that underwent PET at our institution from 2004 to 2009. Results of PET were compared to pathological diagnosis of tonsillectomy (Table 1) or FNA biopsy (Table 2) when available which was performed at physician's discretion. Patients that were diagnosed with lymphoma during restaging studies performed for a different primary malignancy were excluded. Results and Discussion: All 8 tonsillectomies and FNA biopsies performed after a restaging PET that showed increased tonsil uptake were negative for malignancy (Figure 2). All of these 8 patients had an initial previous PET that did not show increased tonsil uptake and also these 8 patients remained in remission from their lymphoma after the procedure was performed. In contrast, 6 out of 7 patients that underwent tonsillectomy or FNA at diagnosis were positive for malignancy (Table 3). Differences among tonsil FDG uptake has been thought to reflect differences in activity of “physiological” inflammation of the palatine tonsils. Increased glucose metabolism during active inflammation in the case of chronic tonsillitis or lymphocyte proliferation in the case of a patient that has received prior chemotherapy (likely experiencing compensatory extra medullar lymphoid hyperplasia) were thought to be causes of high FDG uptake in the tonsils. The significance of such increased tonsil FDG uptake is currently unknown however previous studies suggest that normal pharyngeal palatine tonsil uptake was generally symmetrical and that the difference in maximal standardized uptake value (SUVmax) between right and left tonsils (right-to-left ratio or a surrogate of symmetry) in the same patient might be helpful in detecting malignant tissue. The mean right-to-left ratio of tonsillar SUV was 4.55 in patients with confirmed malignant pathology and 1.53 in patients with documented benign tonsillar tissue (Table 4). The mean tonsillar SUVmax was 15.35 in patients with confirmed malignant pathology and 7.05 in patients with documented benign tonsillar tissue hence SUVmax seems to be useful in differentiating tumor from physiological accumulation. Younger patients with low SUV max symmetric tonsillar uptake and no other abnormal FDG areas seen during restaging PET could probably be watched non-invasively. Conclusions: At the time of initial staging PET, increased tonsil uptake showed true lymphomatous involvement in most cases. At restaging, increased tonsil uptake displayed no cases positive for lymphomatous involvement as all tonsillectomies and FNA biopsies were negative for malignancy. These findings seem to be valid irrespective of the subtype of lymphoma. Our study supports a conservative non-invasive approach because physiologic uptake is the most common cause of increased tonsil uptake when restaging lymphoma patients after treatment has been completed. Disclosures: No relevant conflicts of interest to declare.

Breast cancer remains the second leading cause of malignancy-related death in women in the United States, regardless of advances in novel therapeutic agents. High priority should be emphasized in research aimed at the study of pharmacological and natural compounds that may potentially prevent the development of breast cancer in susceptible patients. Among the known selective estrogen receptor modulators with proven chemopreventive effects, raloxifene has been studied in a number of clinical trials evaluating this drug for the prevention of osteoporosis and coronary heart disease. The MORE and CORE trials had as a primary end point the efficacy of raloxifene in the treatment of women with osteoporosis. These studies showed that raloxifene reduced the risk of invasive breast cancer in postmenopausal women. However, the STAR trial showed no significant difference between raloxifene and tamoxifen recipients in the incidence of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer. This review focuses on the chemopreventive properties of raloxifene and the clinical trials that have proven its efficacy as a chemopreventive agent in invasive breast cancer.