Rhabdomyolysis: a case study exploring the possible side effect of lipid lowering medication by a HIV positive patient taking a protease inhibitor

This case study explores the incidence of rhabdomyolysis in a HIV positive patient that was taking a lipid lowering drug and a protease inhibitor concurrently while under chiropractic treatment for generalized muscular soreness. Dyslipidemia is a very common problem both in the general and HIV population, with many patients being prescribed lipid lowering drugs. While extremely rare, adverse effects of lipid lowering drugs have been documented to include myopathy such as rhabdomyolysis. It is imperative that chiropractors are aware of the possible adverse side effect of lipid lowering drug therapy in their patients complaining of musculoskeletal pain. It is even more important that chiropractors treating the HIV population are aware of the potential interactions between these medications and protease inhibitors to cause myopathy.     

Aromatase inhibitors in the adjuvant treatment of postmenopausal women with early breast cancer: Putting safety issues into perspective

Tamoxifen has been the gold standard adjuvant therapy for the treatment of postmenopausal women with hormone-receptor-positive (HR+) early breast cancer for many years. Tamoxifen treatment is limited to 5 years because of the development of de novo and acquired resistance, and an ongoing risk of adverse events, including endometrial cancer, thromboembolic events, and gynecological symptoms with long-term use. The third-generation aromatase inhibitors (AIs), letrozole, anastrozole, and exemestane, are displacing tamoxifen as the first-choice therapy for HR+ early breast cancer, and are now recommended as the preferred therapy by national and international guidelines. Recent randomized trials have demonstrated that the AIs are more effective than tamoxifen in preventing disease recurrence when used in substitution and sequential strategies in the early adjuvant setting, and letrozole has been shown to be more effective than placebo in the extended adjuvant setting (after 5 years of tamoxifen therapy). Trial safety data show that the overall tolerability of AIs is similar to that of tamoxifen, with adverse events being predictably characteristic of estrogen deprivation; however, some important differences in adverse event profiles between tamoxifen and the AIs have been demonstrated. In addition to antiestrogenic effects, tamoxifen acts as an estrogen agonist in some tissues, which can lead to serious side effects not associated with the AIs, which prevent estrogen biosynthesis. A lower incidence of gynecological and thromboembolic events is observed in patients taking AIs, and fewer cases of endometrial cancer are seen compared with tamoxifen. Adverse events that are more frequent with adjuvant AI therapy compared with tamoxifen include arthralgia and myalgia, bone loss, and effects on the cardiovascular system and blood lipids. The effects of AIs on bone are predictable and may be easily managed, where necessary, with bisphosphonates. Studies examining the effects of AIs on the cardiovascular system and lipid profiles, including in the extended adjuvant setting, suggest that these adverse events may be due to the absence of a protective effect of tamoxifen rather than true AI toxicity. Further studies are required to determine the long-term safety of AI therapy in postmenopausal women with HR+ early breast cancer.     

Renal transplant patients with gastrointestinal intolerability to mycophenolate mofetil: conversion to enteric-coated mycophenolate sodium

The introduction of mycophenolate mofetil (MMF) was an important advance in immunosuppressive therapy, although its use is limited by adverse gastrointestinal events. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed to avoid these side effects. Recent clinical trials have demonstrated that EC-MPS is a safe drug in both de novo and maintenance renal transplant patients. In this prospective study, therapeutically equivalent doses of EC-MPS were administered to 39 stable kidney transplant patients receiving MMF. After 3 months of treatment with EC-MPS the incidence of adverse gastrointestinal events was lower (15.8% of the patients). There were higher levels of mycophenolic acid after conversion to EC-MPS, probably due to better absorption. These factors allowed decreased doses and levels of calcineurin inhibitors without increasing the risk of graft rejection. At 3 months postconversion, serum creatinine improved from the mean baseline value of 1.83 +/- 0.12 mg/dL to 1.70 +/- 0.10 mg/dL. In conclusion, EC-MPS was well tolerated in maintenance renal transplant patients with adverse gastrointestinal events secondary to MMF.     

Translating trial data into patients benefits: making the right choice

Tamoxifen has been the standard first-line adjuvant treatment for postmenopausal women with early breast cancer for over 3 decades. Its use, however, is associated with a number of potentially life-threatening adverse events. As a result, the aromatase inhibitors (AIs), which are generally better tolerated and more efficacious, are now beginning to supersede tamoxifen as the treatment of choice in this setting. Nevertheless, some patients in clinical practice still start or remain on tamoxifen therapy instead of an AI. This review investigates our current understanding of AIs and tamoxifen in the adjuvant hormonal therapy of postmenopausal breast cancer in relation to efficacy, safety and patient benefits. Overall, it is concluded that the AIs show a significant advantage over tamoxifen, with the greatest difference observed at 1-2 years after initiation of treatment. Therefore, using an AI at the earliest opportunity provides patients with the best option to prevent the recurrence and excess adverse events associated with tamoxifen.     

Individualized treatment of hepatitis C virus infection

The current treatment of chronic hepatitis C since several years, the association of pegylated interferon and ribavirine, allows to obtain a virological eradication in around 55% of patients, including 45% of those infected with the genotype 1. The cure, defined by an undetectable viremia 24 weeks after the discontinuation of treatment, is associated to an improvement of the prognosis of the patients with a decrease of mortality and morbidity. If the virologic recovery allows fibrosis regression, including cirrhosis reversal, why not to treat every HCV-infected patient? Because first therapy is not mandatory in all the patients (minim liver disease, co-morbidities which may be contraindications to therapy), second adverse events are frequent and may be severe, third costs are high (the antiviral treatment but also hematological growth factors…) and finally the treated patients do not recover constantly. This has resulted in personalized therapies based on the severity of the disease, the early viral kinetics, pharmacologic monitoring, genetic and immunological factors. In addition to these factors of personalization, the development of new anti-viral C molecules, the protease inhibitors (boceprevir or telaprevir which are about to be approved in combination with pegylated interferon and ribavirine) will allow to achieve a sustained virologic response in around 75% of cases.     

Experience with the treatment of acute pancreatitis with 5-fluorouracil in the light of late results

A comparative analysis of results of treatment of 471 patients with acute pancreatitis after complex therapy including inhibitors of proteases and antimetabolite of 5-ftoruracil has been made. Results of the treatment have shown high effectiveness of 5-ftoruracil which are superior to the effect of protease inhibitors. Remote results of the treatment were followed in 134 patients. Best results were obtained in the group of patients subjected to the complex treatment with 5-ftoruracil.     

Management of sunitinib-related adverse events: an evidence- and expert-based consensus approach

Background  

The advance of medical treatment in renal cell carcinoma (RCC) has fostered the development of diverse continuous oral therapies with tyrosine kinase inhibitors (TKI), among these sunitinib remains the mainstay of therapy for most of the patients. Based on its clinical activity, disease control over a period of 11 months can be expected with sunitinib treatment. Given this prolonged period of exposure to sunitinib, adverse events tend to reoccur and can possibly decrease the quality of life in our patients. Hence, development of modalities to detect, treat and cope with such adverse events has become a major focus for physicians and patients. Today, numerous publications address these questions and offer advice from experienced centers. However, these reviews summarize single or oligo-center experiences.     

Vardenafil: A new approach to the treatment of erectile dysfunction

Vardenafil is a phosphodiesterase type-5 (PDE-5) inhibitor developed as an oral therapy for erectile dysfunction (ED). Multiple phase 3 clinical trials have been completed and vardenafil is expected to launch worldwide in 2003. Two pivotal, randomized, double-blind, multicenter studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement also was noted in other aspects of sexual function, including confidence, orgasmic function, and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity, and etiology and is efficacious for the treatment of ED in diabetic and postprostatectomy patients. Vardenafil has a rapid onset of action and completion of successful sexual intercourse is possible for some patients 16 minutes after its administration. Twenty milligrams of vardenafil has sustained long-term efficacy by providing up to 92% of patients with improved erections during more than 2 years of treatment. Vardenafil is well tolerated, with an adverse event profile typical of the class of PDE-5 inhibitors. The most common adverse events were headache, flushing, rhinitis, and dyspepsia, which were mild or moderate and generally decreased with continued treatment. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo.     

Toxicities Following Treatment with Bisphosphonates and Receptor Activator of Nuclear Factor-κB Ligand Inhibitors in Patients with Advanced Prostate Cancer

ContextAdvanced prostate cancer (PCa) is associated with skeletal complications, both as a result of bone metastases and because of fractures associated with fragility due to androgen-deprivation therapy (ADT). Osteoclast inhibitors are commonly used to reduce skeletal complications but are associated with a number of potential adverse events.ObjectiveTo review clinical trials of osteoclast inhibitors in advanced PCa, to discuss the adverse event profile of these agents, and to discuss strategies to address specific adverse events.Evidence acquisitionPubMed was searched for reports of clinical trials of osteoclast inhibitors in advanced PCa. As zoledronic acid and denosumab are used most commonly in this disease, these trials were the focus. The literature was reviewed to identify key publications addressing the prevention and management of adverse events associated with these drugs.Evidence synthesisThe major findings of the trials and the adverse events are discussed. Prevention and management of common adverse events are addressed.ConclusionsZoledronic acid prevents loss of bone mineral density associated with ADT and delays skeletal-related events in metastatic castration-resistant PCa (mCRPC). Denosumab reduces the incidence of fragility fractures associated with ADT, delays the onset of bone metastases in nonmetastatic castration-resistant disease, and is superior to zoledronic acid in the prevention of skeletal complications in mCRPC. Adverse events associated with both agents include osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab. Zoledronic acid requires dose modifications for renal insufficiency, is contraindicated in severe renal insufficiency, and has been associated with deterioration of renal function. Appropriate patient selection with close attention to dental health, supplementation with calcium and vitamin D, and monitoring of laboratory values are effective strategies to minimize the impact of adverse events associated with osteoclast inhibitors in advanced PCa.     

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment

The last few years important changes have occurred in the field of diabetes treatment. The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors, while individualization of glycemic target is suggested. Furthermore, regulatory authorities now require evidence of cardiovascular (CV) safety in order to approve new antidiabetic agents. The most novel drug classes, i.e., sodium-glucose transporter 2 inhibitors (SGLT2-i) and some glucagon-like peptide-1 receptor agonists (GLP-1 RA), have been demonstrated to reduce major adverse CV events and, thus, have a prominent position in the therapeutic algorithm of hyperglycemia. In this context, the role of previously used hypoglycemic agents, including dipeptidyl peptidase 4 (DPP-4) inhibitors, has been modified. DPP-4 inhibitors have a favorable safety profile, do not cause hypoglycemia or weight gain and do not require dose uptitration. Furthermore, they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes. Still, though, they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA. Overall, DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.     

Adjuvant and extended adjuvant use of aromatase inhibitors: reducing the risk of recurrence and distant metastasis

In patients with early-stage breast cancer, all recurrences are associated with an increased risk of mortality, especially distant metastases. Adjuvant tamoxifen therapy for 5 years is effective in postmenopausal patients for the prevention of disease recurrence but is associated with increased risk of rare, potentially fatal adverse events such as endometrial cancer, stroke, and pulmonary embolism. Recently, randomized clinical trials have shown aromatase inhibitor therapy to be superior to tamoxifen therapy for the prevention of disease recurrence. Switching to an aromatase inhibitor after 2-3 years of tamoxifen treatment has been shown to provide superior disease-free survival compared with completing 5 years of tamoxifen. Among approved aromatase inhibitors (letrozole, anastrozole, and exemestane), letrozole is the only one approved as extended adjuvant therapy after completing 5 years of tamoxifen. These results suggest that 10 years of adjuvant endocrine therapy is superior to 5 years of tamoxifen alone.     

The Oncologist's View: Targeted Therapies in Advanced Renal Cell Carcinoma

Multitargeted therapies, such as tyrosine kinase inhibitors, represent a significant advance in the treatment of metastatic renal cell carcinoma. The clinical benefits of multitargeted agents compared with conventional cytokine therapy have been widely reported. As with other anticancer agents, these newer treatments are associated with side-effects, although the multitargeted agents appear to have a far more favourable safety profile than that of cytokine therapy. Most adverse events (AEs) associated with multitargeted agents are reported as grade 1 or 2 in severity and can be managed appropriately. Nonetheless, efficacy, safety, and the management of AEs must be balanced to ensure that patients receive optimum care and that the duration of therapy can be maintained for an appropriate period. In this review, important factors for consideration in selecting a therapeutic agent are discussed. The role of patient education with regard to reporting AEs, as well as regimen compliance, are of utmost importance and are highlighted here.     

Therapy management of cardiovascular adverse events in the context of targeted therapy for metastatic renal cell carcinoma

Targeted agents have significantly improved outcomes in patients with metastatic renal cell carcinoma, and are changing long‐term expectations in these patients. Experience with these agents highlights a distinct safety and tolerability profile, differing from that observed with conventional chemotherapy and radiotherapy. Cardiovascular adverse events have been observed when treating with targeted agents. This is of particular importance for patients with metastatic renal cell carcinoma who are elderly and present with significant comorbidities. A multidisciplinary approach and close collaboration between oncologists and cardiologists is essential for optimal management of cardiovascular adverse events. Strategies for the management of these adverse events include assessment of cardiovascular status at baseline and at regular intervals, patient education, and the use of supportive medication. Effective therapy management allows patients with cardiovascular adverse events to receive and continue targeted therapy with careful monitoring. Implementation of therapy management measures contributes towards maximizing treatment outcomes with targeted agents in patients with metastatic renal cell carcinoma.     

Interleukin-2 receptor monoclonal antibodies in renal transplantation: current use and emerging regimens

The anti-IL-2R MAbs have been shown to be effective with a variety of immunosuppression regimens including triple therapy with MMF and, more recently, with tacrolimus. They continue to have an excellent safety profile, providing enhanced efficacy with no added adverse events. In emerging regimens that utilize SRL, they may facilitate a successful outcome as well as be sparing of calcineurin inhibitors.     

Use of intravenous bisphosphonates in osteoporosis

Bisphosphonates, which are potent bone resorption inhibitors, currently are the mainstay of treatment for osteoporosis. Antifracture efficacy has been demonstrated for at least three nitrogen-containing bisphosphonates in oral formulations that are designed to be administered in weekly or monthly dosing regimens. Frequent reports of adverse events, primarily related to the upper gastrointestinal tract, and the strict dosing schedule necessary for oral bisphosphonate therapy are considered the major reasons for disappointing adherence to therapy. New intravenous formulations have been developed that allow dosing at very long intervals, thus avoiding the gastrointestinal complications associated with oral bisphosphonates and, it is hoped, improving compliance, particularly for patients who are intolerant of oral bisphosphonates or have contraindications to their use. This alternative approach holds promise for improved outcomes of osteoporosis treatment and ultimately for reduced health care costs related to caring for people with fragility fractures.     

Acute renal dysfunction associated with selective COX-2 inhibitor therapy

The recent release of the selective cyclooxygenase-2 (COX-2) enzyme inhibitors for the treatment of various inflammatory disorders and pain syndromes has been associated with a clear-cut decrease in adverse gastrointestinal effects. The nephrotoxic effect of selective COX-2 inhibitors has not yet been firmly established. We report a case of reversible acute renal failure due to rofecoxib treatment in an elderly patient with several risk factors associated with traditional nonselective nonsteroidal anti-inflammatory drug (NSAID)-related nephrotoxicity. It is prudent to approach therapy with selective COX-2 inhibitors cautiously and in a fashion similar to traditional NSAID therapy for patients with risk factors that induce prostaglandin-dependent renal function.     

肝细胞癌免疫治疗的现状和展望

肝细胞癌因其发病率和病死率较高,已成为关乎全民健康的严重问题。肝细胞癌的治疗方法众多,近年来免疫治疗的兴起为肝细胞癌的治疗提供了新武器,其实用价值亦得到越来越多的肯定和关注。肝细胞癌的免疫治疗经历了最初的细胞毒性药物、小分子抑制剂到现在的免疫检查点抑制剂,促进肿瘤治疗的模式发生重大改变。同时,应重视免疫相关不良事件的管理和治疗,通过建立多学科诊断与治疗团队促进和提高肝细胞癌的综合治疗水平,从根本上提高疗效,造福患者。