Current and future options for the treatment of chemotherapy-induced anaemia

Chemotherapy-induced anaemia (CIA) is a significant source of morbidity in patients receiving treatment for cancer. There are three products currently available for the treatment of CIA: epoetin alfa, epoetin beta and darbepoetin alfa. Several organisations have published recommendations for the use of these agents. Several randomised, controlled trials have been conducted comparing the most popular dosing regimens of epoetin alfa and darbepoetin alfa, with conflicting results. Information regarding survival and adverse event data related to these agents continues to create debate. This review considers four new agents that are under development for the treatment of CIA.     

Current and future treatment options for community-associated MRSA infection

Introduction: Community-associated MRSA (CA-MRSA) represents a global epidemic which beautifully encapsulates the fascinating ability of bacterial organisms to adapt quickly on an evolutionary basis to the extreme selective pressure of antibiotic exposure. In stark contrast to Healthcare-associated MRSA (HA-MRSA), it has become apparent that CA-MRSA is less straight forward of a challenge in terms of controlling its transmission, and has forced clinicians to adjust empiric management of clinical syndromes such as skin and soft tissue infection (SSTI) as well as pneumonia.

Areas covered: This review details the history and epidemiology of CA-MRSA, while covering both current and future treatment options that are and may be available to clinicians. The authors reviewed both historic and more recent literature on this ever-evolving topic.

Expert opinion: While development of new anti-MRSA agents should be encouraged, the importance of antimicrobial stewardship in the battle to stay ahead of the curve with regards to the ongoing control of the MRSA epidemic should be emphasised.     

Current and future treatment options in osteoporosis

Purpose  

The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population.     

Current and future treatment options for esophageal cancer in the elderly

Introduction: Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years).

Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett’s esophagus or early carcinoma, advanced tumor stages, and inoperable cancer.

Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.     

Current and future treatment options for nonexudative and exudative age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the industrialised world. Although relatively simple to diagnose through direct visualisation augmented with rapid sequence fluorescein angiography, treatment has presented a far greater challenge because the true aetiology of AMD is largely unknown. Within the past decade, researchers have introduced many new, potentially promising treatment and prevention options in an attempt to minimise the damage imparted from AMD. They capitalise on many of the theoretical and known factors contributing to AMD progression. A high-dose of an orally administered combination of the antioxidants ascorbic acid (vitamin C), tocopherol (vitamin E) and beta-carotene, in addition to copper and zinc, is the only widely accepted preventive therapy. Thermal laser photocoagulation and verteporfin photodynamic therapy are the only standard treatment options available based on large scale, randomised, prospective, placebo-controlled trials; however, efficacy is limited and only a minority of patients who present with AMD are eligible for these treatments. Many other preventive and treatment options are in all phases of clinical studies and expected to change the entire approach to AMD management in the near future. For example, alternative antioxidants, drusen ablation, apheresis and HMG-CoA reductase inhibitors have shown promise in some studies by preventing or slowing the progression of certain forms of AMD. In addition, alternative photodynamic therapies, low-intensity laser, antiangiogenic medications, radiation treatment and surgery have demonstrated the ability, albeit to differing degrees, to inhibit or possibly even reverse the severe vision loss often associated with AMD characterised by choroidal neovascularisation.     

The use of darbepoetin alfa for the treatment of chemotherapy-induced anaemia

Chemotherapy-induced anaemia, with its important consequences on quality of life and social function of cancer patients, can be improved with erythropoietic therapy. Darbepoetin alfa is the first of a novel generation of erythropoietic proteins with a unique molecular structure and a circulating half-life that is threefold longer than that of the previous recombinant human erythropoietin. The efficacy and safety of weekly administration have been confirmed in different Phase II and III randomised trials. In order to optimise the efficacy profile of darbepoetin alfa, extended dosing intervals and front-loading regimens are evaluated, as well the optimal haemoglobin level to initiate therapy. Across all trials, darbepoetin alfa was shown to be a well-tolerated and safe therapy. The possible favourable effect on the outcome of cancer patients needs to be further elucidated.     

Pharmacotherapy of chemotherapy-induced anaemia

Anaemia in cancer patients is multifactorial. Anaemia of chronic disease due to the effects of cancer, as well as side effects of cancer treatment, are important factors. The impact of anaemia on the quality of life and social function of cancer patients has recently become more acknowledged. The traditional treatment for chemotherapy-induced anaemia (CIA) has been the use of red blood cell transfusions, with only short-lived effects and all their inherent risks. The finding of deficiency in erythropoietin, the endogenous hormone responsible for the production and maintenance of red blood cells in these patients, was the basis for the therapeutic development of erythropoietic proteins. With the introduction of epoetins (recombinant forms of human erythropoietin) in oncology and more recently, the novel long-acting darbepoetin alpha, physicians gained new pharmacotherapeutic approaches to treat CIA. Several forms of erythropoietic proteins are available in various regions of the world. Their characteristics, clinical evidence for use, guidelines for clinical administration and their safety are described in this review.     

Current treatment options for tendinopathy

Importance of the field: Tendon disorders are frequent and are responsible for much morbidity, both in sport and the workplace. Although several therapeutic options are routinely used, very few well-conducted randomised prospective, placebo, controlled trials have been performed to assist in choosing the best evidence-based management.

Areas covered in this review: We performed a comprehensive search of PubMed, Medline, Cochrane, CINAHL, and Embase databases over the years 1966 – 2010 to review the best evidence-based options for the management of patients with tendinopathy.

What the reader will gain: The reader will obtain information on the available medical and surgical therapies used to manage tendinopathy-related symptoms. The effectiveness of therapies, the length of management and the adverse effects are examined.

Take-home message: Management of tendinopathy is often anecdotic and lacking well-researched scientific evidence. Teaching patients to control the symptoms may be more beneficial than leading them to believe that tendinopathy is fully curable.     

Current treatment options for hyperprolactinemia

Introduction: Hyperprolactinemia is a prevalent cause of oligo-amenorrhea, and prolactinomas are the most common type of functional pituitary tumor. Untreated hyperprolactinemia can lead to bone loss and impair gonadal function and fertility. Normalization of prolactin improves bone mass and restores gonadal function in a majority of patients.

Areas covered: This article contains an overview of hyperprolactinemia with an emphasis on pharmacologic, surgical and radiation treatment options. Discussion focuses on the efficacy and safety of available treatments and comments on new and emerging therapies.

Expert opinion: Dopamine agonists, usually cabergoline, remain the primary choice for initial treatment of hyperprolactinemia. Surgery may also be an appropriate alternative in certain circumstances. Monotherapy with dopamine agonists is often successful at controlling prolactin levels and tumor size, but adjunctive treatments may be necessary for resistant or aggressive prolactinomas.     

Current treatment options for insomnia

Patient complaints of insomnia continue to perplex many physicians because of the vast array of potential causes and multiple strategies to treat this symptom complex. The present review summarizes available pharmacological and nonpharmacological interventions for insomnia. A specialized assessment and treatment plan is required for all patients, taking into account all aspects of their life and the characteristics of their sleep disturbance.     

Pharmacotherapy of chemotherapy-induced anaemia

Anaemia in cancer patients is multifactorial. Anaemia of chronic disease due to the effects of cancer, as well as side effects of cancer treatment, are important factors. The impact of anaemia on the quality of life and social function of cancer patients has recently become more acknowledged. The traditional treatment for chemotherapy-induced anaemia (CIA) has been the use of red blood cell transfusions, with only short-lived effects and all their inherent risks. The finding of deficiency in erythropoietin, the endogenous hormone responsible for the production and maintenance of red blood cells in these patients, was the basis for the therapeutic development of erythropoietic proteins. With the introduction of epoetins (recombinant forms of human erythropoietin) in oncology and more recently, the novel long-acting darbepoetin alpha, physicians gained new pharmacotherapeutic approaches to treat CIA. Several forms of erythropoietic proteins are available in various regions of the world. Their characteristics, clinical evidence for use, guidelines for clinical administration and their safety are described in this review.     

Current treatment options for myeloma

In most cases multiple myeloma is an incurable plasma cell malignancy. Despite the use of conventional therapy or high-dose chemotherapy with autologous stem cell transplantation (ASCT), patients continue to relapse at a constant rate. A small minority of patients are cured by allogeneic transplantation. Novel drugs targeting not only the myeloma cell but also its interactions with the malignant microenvironment have recently been used in patients with relapsed/refractory disease. So far, ASCT has been the treatment of choice for eligible myeloma patients. However, many questions regarding the management of myeloma patients remain unanswered. How safe is ASCT in elderly patients? Is there a role for non-myeloablative allogeneic transplantation in multiple myeloma? What is the role of novel agents, such as thalidomide, its analogues and bortezomib, in the treatment of newly diagnosed patients or as maintenance post-ASCT? This review summarises all available data for the current treatment options for myeloma providing a useful algorithm for its management.     

Therapeutic effects of epoetin zeta in the treatment of chemotherapy-induced anaemia

ABSTRACT

Objective: To perform an open, non-controlled, multiple-dose, international, multicentre, phase III study to evaluate epoetin zeta, a biosimilar epoetin referenced to epoetin alfa, for the treatment of chemotherapy-induced anaemia in patients with cancer.

Methods: Safety, tolerability and efficacy of subcutaneously administered epoetin zeta were assessed in 216 patients with solid tumours or non-myeloid haematological malignancies receiving chemotherapy and at risk of transfusion.

Results: A significant (p?<?0.0001) increase in mean haemoglobin (Hb) level (1.8?g/dL) was observed between baseline and week 12 (intent-to-treat population); 176/216 (81.5%) patients achieved a response (increase in Hb?≥?1?g/dL or reticulocyte count ≥40?000 cells/μL) by week 8. Over the treatment period, 231 treatment-emergent adverse events were experienced by 91 patients; 9/216 (4.2%) experienced a clinically significant thrombotic event within the first 12 weeks of epoetin zeta treatment, significantly lower than the assumed 18% baseline incidence (p?<?0.0001) based on historical data from epoetin trials. No transfusion was necessary for 175/216 patients (81.0%) and quality of life improved over the study. No patients developed anti-erythropoietin antibodies. Sponsor trial no: CT-830-05-0009.

Conclusion: This study demonstrates that subcutaneously administered epoetin zeta is well-tolerated and has efficacy in the treatment of anaemia in patients with cancer receiving chemotherapy and at risk of transfusion.     

Current and potential treatment options for hyperphosphatemia

Introduction: Hyperphosphatemia is common in late stages of chronic kidney disease and is often associated with elevated parathormone levels, abnormal bone mineralization, extra-osseous calcification, and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control plasma phosphorus levels. Although effective at lowering serum phosphorus, they all have safety, tolerability, and compliance issues that need to be considered when selecting which one to use.

Areas covered: This paper reviews the most established treatment options for hyperphosphatemia, in patients with chronic kidney disease, focusing on the new inhibitors of active phosphate absorption.

Expert opinion: The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Nonetheless, an extending range of phosphate binders are now available. Aluminum has potentially serious toxic risks. Calcium-based binders are very effective but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, and long-term effects of tissue deposition seem clinically irrelevant. Sevelamer, appear to have profiles that would lead to pleiotropic effects and reduced progression of vascular calcification, and the main adverse events seen with these agents are gastrointestinal. Iron has a powerful capability of binding phosphate, thus numerous preparations are available, both with and without significant systemic absorption of the iron component. The inhibitors of active intestinal phosphate transport, with their very selective mechanism of action and low pill burden seem the most interesting approach; however, do not seem at present to be effective alone, in reducing serum phosphorus levels.     

Current and emerging treatment options for endometriosis

Introduction: Pharmacotherapy has a pivotal role in the management of endometriosis with long-term treatments balancing clinical efficacy (control of pain symptoms and prevention of recurrence of the disease after surgery) with an acceptable safety profile. Treatment choice is based on several factors including age and patient preference, reproductive plans, intensity of pain, severity of disease and incidence of adverse effects.

Areas covered: The aim of this review is to provide the reader with a complete overview of drugs that are currently available or are under investigation for the treatment of endometriosis highlighting on-going clinical trials.

Expert opinion: Almost all of the available treatment options for endometriosis suppress ovarian function and are not curative. Combined oral contraceptives and progestins are commonly administered to these patients in order to ameliorate pain symptoms. Gonadotropin-releasing hormone-agonists are prescribed when first-line therapies are ineffective, not tolerated or contraindicated. Aromatase inhibitors should be reserved only for women who are refractory to other treatments. Amongst the drugs under development, gonadotropin-releasing hormone antagonists have shown the most promising results. Presently, are a number of potential therapies currently in pre-clinical or early clinical studies which may alter treatment strategies in the future although further studies are necessary.     

Current and future contraceptive options for women living with HIV

Introduction: Among women living with HIV, half of the pregnancies are unintended. Effective contraception can prevent unintended pregnancies and consequently reduce maternal mortality and perinatal transmission of HIV. While contraceptive options available for all women also apply to women living with HIV, specific considerations exist to the use of contraception by women living with HIV.

Areas covered: First, general principles guiding the use of contraception among women living with HIV are discussed, such as choice, method mix, relative effectiveness, and drug-drug interactions. Second, a detailed discussion of each contraceptive method and issues surrounding the use of that method, such as drug-drug interactions, follows. Third, future contraceptive options in advanced development for use by women or men are briefly discussed.

Expert opinion: Contraceptive methods available to all women should also be accessible to women living with HIV. When the relative effectiveness of a contraceptive method is reduced, for example due to drug-drug interactions with antiretrovirals, the method should still be made available to women living with HIV with the appropriate information sharing and counseling. Greater research on various aspects of contraceptive use by women living with HIV and more comprehensive testing of co-administration of hormonal contraceptives and common medications used by these women are warranted.     

Current options for the treatment of systemic scleroderma

The epidemiology, pathology, diagnosis, and clinical manifestations of systemic scleroderma (SSc) are described, and therapeutic options are discussed. SSc is a rare condition of unknown etiology that occurs in a subset of scleroderma patients. It is distinguished by involvement of the small arteries, microvessels, and diffuse connective tissue. The degree of internal organ involvement is the main determinant of morbidity and mortality. Management of SSc may entail supportive, palliative, remittive, and immunosuppressive therapies. Supportive therapy involves maintaining the affected extremities at warm temperatures and the use of emollient creams. Results of palliative treatment are mixed. Toxic reactions may be associated with many of these medications. Dermatologic manifestations have been treated with nonsteroidal anti-inflammatory agents, low-dose corticosteroids, dimethyl sulfoxide, and edetate disodium; peripheral and internal-organ vascular obstruction, with alpha-adrenergic blockers, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. Antacids with alginic acid, histamine H2-receptor antagonists, sucralfate, and cholinergic-acting agents may be used to relieve GI symptoms. Lung infections should be treated promptly with antibiotics. No drug therapy has been successful in reducing the incidence of fatal cardiac arrhythmias or in preventing cardiac fibrosis. Captopril and enalapril are essential in the control of SSc renal crisis. Penicillamine may hold promise as a remittive therapy. The immunosuppressive agents fluorouracil, cyclosporine, and methotrexate, which have shown limited effectiveness in preliminary studies, merit further investigation. No therapeutic agent has yet been shown to alter the course of SSc on a consistent or long-term basis. Toxicity and drug interactions remain a major concern in patient management, and aggressive monitoring is essential.     

Current treatment options for neuroendocrine tumors

Neuroendocrine tumors are heterogeneous in their clinical behavior and require therapies specially tailored according to staging and grading, origin and expression of peptide receptors. Somatostatin analogues act as antisecretory and antiproliferative agents. Chemotherapy is mandatory for poorly differentiated neuroendocrine carcinomas and is also effective in neuroendocrine tumors of the pancreas and of the bronchial system. For localized neuroendocrine tumors, surgery should be performed with curative intent and is also an option in advanced or metastasized neuroendocrine tumors with the goal to debulk tumor masses. Local ablative therapies may be applied to decrease tumor load in the liver; however, results are often of short duration. Peptide receptor radiotherapy is a new treatment method applying radionuclide-targeted somatostatin receptor agonists for internal cytotoxic radiotherapy in somatostatin receptor-expressing neuroendocrine tumors. Retrospective and prospective clinical studies indicate prolonged progression-free survival and overall survival of patients responding by stable disease or any kind of remission with this innovative treatment, which is, however, available only in a few specialized centers. Finally, small-molecule inhibitors of vascular endothelial growth factor and serine/threonine-protein kinase mTOR pathways have been shown to delay progression in patients with neuroendocrine tumors. In summary, treatment options for neuroendocrine tumors have expanded considerably in the last years leading to prolonged overall survival.     

Current treatment options for acute pain

The pain that accompanies surgical procedures remains prevalent and is an aspect of the perioperative experience that generates the greatest concern for patients about to undergo surgery. There is also a growing recognition of the extent that acute painful experiences can lead to longer-term painful consequences, even when tissue healing appears to be complete. The neurobiologic basis of this has been partially elucidated. The key observations are that multiple sites and multiple receptors collectively contribute, and that noxious stimuli initiate a cascade of events that sensitise the nervous system so that subsequent noxious stimuli are perceived with greater intensity and even previously non-painful stimuli can be painful. Incorporating these observations into effective perioperative regimens designed to limit acute pain and its consequences leads to a multimodal pre-emptive approach to acute pain management. Acute perioperative pain is an ideal setting for the use of pre-emptive analgesic techniques because the timing of noxious stimuli is known in advance and surgical sensitisation of the nervous system is ongoing despite adequate levels of general anaesthesia with volatile anaesthetics. The relevant neurobiology of pain, reviewed in this article, is the basis for advocating an aggressive, multimodal, pre-emptive approach to acute pain therapy throughout the entire perioperative period. A growing body of outcome studies demonstrates the long-term efficacy of this approach.