Meta-analysis of cardiovascular toxicity risks in cancer patients on selected targeted agents.

PURPOSE: The purpose was to estimate the risk and severity of cardiovascular toxicities associated with selected targeted agents. METHODS: We searched English-language literature for randomized clinical trials published between January 1, 2000 and November 30, 2013 of targeted cancer therapy drugs approved by the FDA by November 2010. One hundred ten studies were eligible. Using meta-analytic methods, we calculated the relative risks of several cardiovascular toxicities [congestive heart failure (CHF), decreased left ventricular ejection fraction (DLVEF), myocardial infarction (MI), arrhythmia, and hypertension (HTN)], adjusting for sample size using the inverse-variance technique. For each targeted agent and side effect, we calculated the number needed to harm. RESULTS: Regarding CHF, trastuzumab showed significantly greater risk of all-grade and high-grade CHF. There was significant increased risk of all-grade DLVEF with sorafenib, sunitinib, and trastuzumab and high-grade DLVEF with bevacizumab and trastuzumab. Sorafenib was associated with significant increased all-grade risk of MI based on one study. None was associated with high-grade risk of MI or increased risk of arrhythmia. Bevacizumab, sorafenib, and sunitinib had significant increased risk of all-grade and high-grade HTN. CONCLUSIONS: Several of the targeted agents were significantly associated with increased risk of specific cardiovascular toxicities, CHF, DLVEF, and HTN. Several had significant increased risk for high-grade cardiovascular toxicities (CHF, DLVEF, and HTN). Patients receiving such therapy should be closely monitored for these toxicities and early and aggressive treatment should occur. However, clinical experience has demonstrated that some of these toxicities may be reversible and due to secondary effects.

A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer.

BACKGROUND: Cancer patients receiving chemotherapy are at increased risk for thrombosis. Apixaban, a factor Xa inhibitor, is oral and does not require laboratory monitoring. OBJECTIVES: A pilot study was conducted to evaluate whether apixaban would be well tolerated and acceptable in cancer patients receiving chemotherapy. PATIENTS/METHODS: Subjects receiving either first-line or second-line chemotherapy for advanced or metastatic lung, breast, gastrointestinal, bladder, ovarian or prostate cancers, cancer of unknown origin, myeloma or selected lymphomas were randomized to 5 mg, 10 mg or 20 mg once daily of apixaban or placebo in a double-blind manner for 12 weeks. Use of the study drug began within 4 weeks of the start of chemotherapy. The primary outcome was either major bleeding or clinically relevant non-major (CRNM) bleeding. Secondary outcomes included venous thromboembolism (VTE) and grade III or higher adverse events related to the study drug. Thirty-two patients received 5 mg, 30 patients 10 mg, 33 patients 20 mg, and 30 patients placebo. In these groups, there were 0, 0, 2 and 1 major bleeds, respectively. The corresponding data for CRNM bleeds were 1, 1, 2, and 0. The rate of major bleeding in the 93 apixaban patients was 2.2% (95% confidence interval 0.26-7.5%). There were no fatal bleeds. Three placebo patients had symptomatic VTE. CONCLUSIONS: Apixaban was well tolerated in our study population. These results support further study of apixaban in phase III trials to prevent VTE in cancer patients receiving chemotherapy.

A fatigue clinic in a comprehensive cancer center: design and experiences.

Cancer-related fatigue is now the most prevalent symptom of cancer, occurring in 60-90% of patients. Fatigue has been identified by cancer patients as a factor influencing functionality and quality of life. Our objectives in developing a fatigue specialty clinic at The University of Texas M. D. Anderson Cancer Center were to improve our patients' quality of life by decreasing fatigue; educate health care providers, patients, and patients' families about cancer-related fatigue; develop an appropriate clinical and diagnostic evaluation for this symptom; correlate objective measures of fatigue with its clinical evaluation; and develop innovative treatment plans for cancer-related fatigue. This article describes the general clinic design and operations and the preliminary analysis of the first 40 patients evaluated in the fatigue clinic.

Identifying risk factors for imminent death in cancer patients with acute dyspnea.

A substantial proportion of cancer patients presenting to an emergency center (EC) or clinic with acute dyspnea survives fewer than 2 weeks. If these patients could be identified at the time of admission, physicians and patients would have additional information on which to base decisions to continue therapy to extend life or to refocus treatment efforts on palliation and/or hospice care alone. The purpose of this study was to identify risk factors for imminent death (survival

Severity of illness, outcomes, and resource use in elderly cancer patients with deep venous thrombosis.

Low-molecular-weight heparins provide new options for outpatient management of deep venous thrombosis. Because elderly patients with cancer are at increased risk of developing deep venous thrombosis, outpatient therapy for treatment of deep venous thrombosis may be important in this population. We compared the severity of illness, outcomes, and cost of deep venous thrombosis in elderly patients with cancer to those seen in younger patients with cancer. We examined all 766 episodes of deep venous thrombosis treated at the University of Texas M.D. Anderson Cancer Center between January 1, 1994 and December 31, 1996. Severity of illness level and predicted risks of mortality and readmission were obtained from a commercially available disease staging system (Inforum System). Observed outcomes and cost were based on data collected from the 766 episodes of deep venous thrombosis at our institution. One hundred nineteen (16%) episodes of deep venous thrombosis occurred in patients 70 years of age or older. The severity of illness scale (1-5, least-most severe) were identical (3.7) in the 3 groups studied (< 70 years, 70-79, years and > or = 80 years). The predicted risk of death during hospitalization (6%, 9%, 8%, respectively, by group, P = 0.12) and readmission in 30 days (5%, 4%, 3%, respectively, P = 0.04) were similar among the groups. The observed death rates during hospitalization were 5%, 6%, and 6%, respectively (P = 0.91), and the rates of hospitalization for deep venous thrombosis recurrence were 22%, 16%, and 28%, respectively (P = 0.27). The similarities in outcomes and resource use between elderly and younger patients suggest that elderly patients with cancer are not at greater risk of serious clinical outcomes or a prolonged clinical course. There is significant potential for outpatient management of these patients.

Medical futility and appropriate medical care in patients whose death is thought to be imminent.

Often it is very difficult to make decisions involving the termination of aggressive cancer care in the case of patients who are no longer benefiting. Among these patients, our ability to "do everything possible" to continue life is in conflict with "doing the right thing"; the greatest benefit to these patients derives from delivering excellent supportive care and assisting them in understanding and accepting end-of-life issues. Furthermore, in a cost-conscious environment with limited resources, all patients and, indeed, all of society, benefit when aggressive and often costly cancer care is limited to those patients who are likely to benefit. However, these issues are complex, blending treatment science and ethics, and thus, the physician frequently has no objective reference point on which to base the decisions. This paper integrates the principles of ethics (respect for autonomy, beneficence, nonmaleficence, and justice) and three difficult issues encountered by physicians in clinical decision-making in terminal cancer patients in the American healthcare system. These issues include: medical futility and appropriate care, applications of outcomes research in clinical decision-making, and impact of cost, particularly in a managed care environment, on treatment choice. These topics are illustrated with reference to patients presenting to our emergency center with stage IV lung cancer and dyspnea, and the application of an outcomes model under development to predict imminent death in these patients is discussed. Outcomes models may provide patients, their families, and their physicians with objective data on which to base end-of-life decision-making. Minimizing aggressive treatment of terminally ill patients may provide better life quality and will reduce costs during the patients' end of life. Ethics plays a crucial role in integrating medical science, patient choice, and cost in making appropriate decisions.

Hyperphosphatemia associated with phosphorus-containing laxatives in a patient with chronic renal insufficiency.

A patient with chronic renal insufficiency had hyperphosphatemia, hypocalcemia, hypomagnesemia, hypokalemia, metabolic acidosis, and QT prolongation on electrocardiogram after taking prescribed laxatives containing phosphorus. Clinical findings included tetany in the form of Chvostek's and Trousseau's signs. Symptoms resolved after careful rehydration and electrolyte replacement. The interactions between these electrolytes are described. Patients with moderate to severe renal dysfunction should avoid use of laxatives containing phosphorus. If these laxatives are used in patients with mild renal dysfunction, careful monitoring is indicated.

Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer.

Until recently, febrile neutropenic patients were treated with intravenous antibiotics in inpatient settings. Because of work completed in the last several years by various investigators, identification of a low-risk group of febrile, neutropenic patients has allowed successful treatment with both parenteral and oral antibiotics in an ambulatory environment. This accomplishment has been facilitated by advances in broad-spectrum antibiotics with long half-lives and stabilities, the introduction of the quinolones providing oral antipseudomonal activity, home health care, improvements in vascular access devices, and technically enhanced antibiotic delivery systems. This review focuses on the rationale of risk stratification and the progress made in treating low-risk febrile neutropenic patients as outpatients.

Dyspnea in cancer patients. Etiology, resource utilization, and survival-implications in a managed care world.

BACKGROUND: Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom. METHODS: The authors randomly selected 122 of 1068 patients presenting with dyspnea for a retrospective analysis. The median age of the patients was 58 years (range, 23-90 years) and 53% were female. Underlying malignancies were breast cancer (30%), lung cancer (37%), and other cancers (34%). Approximately 94% of the patients had received prior cancer treatment and the majority (69%) had uncontrolled, progressive disease. RESULTS: The most common treatments administered in the ED were oxygen (31%), beta-2 agonists (14%), antibiotics (12%), and narcotics (11%). Approximately 60% of patients were admitted to the hospital from the ED for further treatment of dyspnea and the underlying malignancy, and the median length of stay was 9 days. The median overall survival after the ED visit for dyspnea was 12 weeks. Specific diagnoses were associated with different median survival rates: lung cancer patients: 4 weeks; breast cancer patients: 22 weeks (P = 0.0073, vs. lung cancer); and other cancer diagnoses: 27 weeks (P = 0.0027, vs. lung cancer). CONCLUSIONS: Lung cancer patients presenting to the ED with dyspnea have much shorter survival than patients with other malignancies. For some patients, the presence of dyspnea requiring emergency treatment may indicate a phase in their illness in which resources should be shifted from acute intervention with hospitalization to palliative and supportive care measures.

Outpatient antibiotic treatment in low-risk febrile neutropenic cancer patients.

Traditionally febrile neutropenic patients have been treated with parenteral antibiotics in an inpatient setting; however, recent work by several investigators has demonstrated successful treatment with both parenteral and oral antibiotics in an ambulatory environment. This has been accomplished by identification of low-risk neutropenic patients, advances in broad-spectrum antibiotics with long half-lives and stabilities, the introduction of the oral quinolones, home health-care initiatives, improvements in vascular access devices, and development of technically enhanced antibiotic delivery systems. Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients should now be considered an acceptable alternative to hospital-based treatment. This review focuses on the development and rationale of risk stratification and examines the results of various outpatient antibiotic trials recently completed.

Causes and management of superior vena cava syndrome.

Superior vena cava syndrome is today primarily a disease associated with malignancy. Thrombosis of the superior vena cava associated with the use of intravascular devices or extraluminal obstruction from malignancy is now recognized as an important pathophysiologic process in the syndrome. Irradiation has long been the mainstay of treatment. Newer treatments include more effective chemotherapy for certain cancers such as lymphoma and small-cell carcinoma, fibrinolytics to treat thrombosis, and interventional radiologic techniques. Expandable metallic stents have been shown to improve the quality of life for patients who, in the past, quickly succumbed to the disease process. Current management stresses the importance of accurate diagnosis of the underlying etiology before treatment. Only under extreme emergent conditions such as laryngeal or cerebral edema should irradiation proceed without a diagnosis. Future studies should address the role of anticoagulant therapy and the timing of interventional techniques in relation to radiation or chemotherapy.