Liposomal amphotericin B (AmBisome) is a lipid-associated formulation of the broad-spectrum polyene antifungal agent amphotericin B. It is active against clinically relevant yeasts and moulds, including Candida spp., Aspergillus spp. and filamentous moulds such as Zygomycetes, and is approved for the treatment of invasive fungal infections in many countries worldwide. It was developed to improve the tolerability profile of amphotericin B deoxycholate, which was for many decades considered the gold standard of antifungal treatment, despite being associated with infusion-related events and nephrotoxicity. In well controlled trials, liposomal amphotericin B had similar efficacy to amphotericin B deoxycholate and amphotericin B lipid complex as empirical therapy in adult and paediatric patients with febrile neutropenia. In addition, caspofungin was noninferior to liposomal amphotericin B as empirical therapy in adult patients with febrile neutropenia. For the treatment of confirmed invasive fungal infections, liposomal amphotericin B was more effective than amphotericin B deoxycholate treatment in patients with disseminated histoplasmosis and AIDS, and was noninferior to amphotericin B deoxycholate in patients with acute cryptococcal meningitis and AIDS. In adults, micafungin was shown to be noninferior to liposomal amphotericin B for the treatment of candidaemia and invasive candidiasis. Data from animal studies suggested that higher dosages of liposomal amphotericin B might improve efficacy; however, in the AmBiLoad trial in patients with invasive mould infection, there was no statistical difference in efficacy between the standard dosage of liposomal amphotericin B 3 mg/kg/day and a higher 10 mg/kg/day dosage, although the standard dosage was better tolerated. Despite being associated with fewer infusion-related adverse events and less nephrotoxicity than amphotericin B deoxycholate and amphotericin B lipid complex, liposomal amphotericin B use is still limited to some extent by these adverse events. Both echinocandins were better tolerated than liposomal amphotericin B. The cost of liposomal amphotericin B therapy may also restrict its use, but further pharmacoeconomic studies are required to fully define its cost effectiveness compared with other antifungal agents. Based on comparative data from well controlled trials, extensive clinical experience and its broad spectrum of activity, liposomal amphotericin B remains a first-line option for empirical therapy in patients with febrile neutropenia and in those with disseminated histoplasmosis, and is an option for the treatment of AIDS-associated cryptococcal meningitis, and for invasive Candida spp. or Aspergillus spp. infections. Amphotericin B, a macrocyclic, polyene antifungal agent, is thought to act by binding to ergosterol, the principal sterol in fungal cell membranes and Leishmania cells. This results in a change in membrane permeability, causing metabolic disturbance, leakage of small molecules and, as a consequence, cell death. In vitro and in vivo studie...
Imatinib (Gleevec, Glivec) is a synthetic tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia (CML). It is specifically designed to inhibit the breakpoint cluster region (BCR)-Abelson (ABL) fusion protein that results from the chromosomal abnormality known as the Philadelphia chromosome. CML is characterised by this abnormality, which leads to abnormalities of the peripheral blood and bone marrow including an increase in the number of granular leukocytes. Imatinib is approved in numerous countries worldwide for the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase CML, Ph+ accelerated-phase or blast-crisis CML, and in patients with Ph+ chronic-phase CML who have failed to respond to interferon-alpha therapy. It is also indicated in paediatric patients with newly diagnosed Ph+ chronic-phase CML, in accelerated-phase or blast-crisis CML, or in chronic-phase CML after failure of interferon-alpha therapy or when the disease has recurred after haematopoietic stem cell transplantation (HSCT). Approved indications, however, may vary by country. Imatinib is effective and generally well tolerated in patients with Ph+ CML. In patients with newly diagnosed chronic-phase CML, imatinib was more effective than interferon-alpha plus cytarabine in preventing progression of the disease and in achieving haematological and cytogenetic responses. Overall survival rates remain high after 5 years of follow-up, and historical comparisons with other treatments demonstrate improved overall survival with imatinib in the long term. Patients with accelerated-phase or blast-crisis CML, or those who have not responded to prior interferon-alpha therapy also benefit from imatinib treatment. Some patients become resistant or intolerant to imatinib therapy; management strategies to overcome these problems include dosage adjustment, other treatments, or combination therapy with imatinib and other agents. Allogeneic HSCT is currently the only potentially curative treatment, but it is associated with high rates of morbidity and mortality and is not suitable for all patients. The introduction of imatinib has had a marked impact on outcomes in patients with CML. It remains a valuable treatment for all stages of the disease, especially initial treatment of newly diagnosed Ph+ chronic-phase CML, and is endorsed by European and US treatment guidelines as a first-line option.
Denosumab (Prolia®) is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the US, the EU and several other countries. Denosumab has a novel mechanism of action; it binds to receptor activator of nuclear factor κB ligand and inhibits bone resorption by inhibiting osteoclast formation, function and survival. In postmenopausal women with osteoporosis, denosumab reduced the risk of vertebral, nonvertebral and hip fractures compared with placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal women with low bone mineral density (BMD) or osteoporosis, treatment with denosumab increased BMD and decreased markers of bone turnover more than alendronate in those who were essentially treatment-naive in the 1-year DECIDE study and also in the 1-year STAND study, in which women were switched from alendronate to denosumab or continued alendronate treatment. Denosumab was generally well tolerated in clinical trials, although long-term effects of very low bone turnover remain to be established. Denosumab is administered once every 6 months via subcutaneous injection, which may be a preferred method of administration and may improve adherence to treatment compared with other osteoporosis treatments. Denosumab is a valuable new option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, and may be useful as a first-line treatment in women at increased risk of fractures who are unable to take other osteoporosis treatments.
Vinflunine is a novel bifluorinated vinca alkaloid that appears to differ from other class members in terms of its tubulin-binding properties and inhibitory effects on microtubule dynamics. Notably, it demonstrated superior in vivo antitumour activity to that of vinorelbine in a range of transplantable murine and human tumours. In a randomized, open-label, multicentre phase III trial in adult patients with advanced transitional cell carcinoma of the urothelium who experienced progression after first-line platinum-containing chemotherapy (n = 370), median overall survival (OS; primary endpoint) was 6.9 months for intravenous vinflunine plus best supportive care (BSC) recipients versus 4.6 months for BSC alone recipients in the intent to treat (ITT) population. The difference in OS between treatment groups was not significant in the ITT population; however, there was a significant improvement in OS for vinflunine plus BSC recipients in the ITT population after adjusting for prespecified prognostic factors, and in the analysis of the eligible population (ITT population excluding baseline protocol violations). In the latter, median OS was 6.9 months with vinflunine plus BSC versus 4.3 months with BSC alone after a median follow-up of approximately 1.8 years and again after a median follow-up of approximately 3.6 years. Progression-free survival, objective response rate and disease control rate were significantly improved with vinflunine plus BSC versus BSC alone. The most frequent treatment-related adverse events in vinflunine recipients included myelosuppression (e.g. neutropenia) and gastrointestinal symptoms (e.g. constipation). In general, adverse events with vinflunine were noncumulative and medically manageable.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.