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Infectious Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Vas Novelli, Delane Shingadia, Huda Al-Ansari
This is a rare AIDS-defining illness in children. It usually presents as a lymphadenopathic variant with massive enlargement of groups of lymph nodes (Fig. 3.31). Progressive visceral involvement may occur as well as skin infiltration (Fig. 3.32). Recurrent blood-stained pleural effusions, indicating pulmonary/pleural Kaposi’s sarcoma, is one manifestation of visceral disease (Fig. 3.33). The disease is now thought to be associated with a new herpes virus (HHV-8). Treatment in children has consisted of administration of various chemotherapeutic agents: Vincristine, bleomycin and doxorubicin.Liposomal daunorubicin.Interferon-alpha.
COP-X (cyclophosphamide, vincristine [Oncovin®], prednisolone/liposomal daunorubicin [DaunoXome®])
Published in Maxwell Summerhayes, Susanna Daniels, Practical Chemotherapy, 2018
Maxwell Summerhayes, Susanna Daniels
Monitor the total dose of liposomal daunorubicin administered. Alert the prescriber if this exceeds 320 mg/m2 (unless there is evidence that cardiac function has been checked at this point and is acceptable). Thereafter, it is important that the left ventricular ejection fraction is checked regularly – after every alternate cycle of treatment is probably reasonable (see Notes for prescribers above). If you are unclear whether monitoring is being carried out or what the schedule is, discuss this with the appropriate member of the medical team. It is especially important when a patient starts a course of treatment to check the pharmacy records and patient notes to ascertain whether they have received previous therapy. The contribution of other anthracyclines should be considered (e.g. doxorubicin) (normal cumulative maximum dose 450 mg/m2).
Overview of HIV Infection
Published in Mark J. Rosen, James M. Beck, Human Immunodeficiency Virus and the Lung, 1998
Kaposi's sarcoma responds to a variety of single agents, including vincristine, vinblastine, bleomycin, doxorubicin, and possibly epirubicin (24). Most responses, however, are partial and short-lived. Higher response rates can be obtained with combination chemotherapy, which leads to a longer disease-free interval and, in pulmonary KS, has also led to improved survival (46). In a retrospective review of patients with disseminated pulmonary KS treated with cytotoxic chemotherapy (doxorubicin, bleomycin, and vincristine), 80% had complete or partial remissions. Median survival for responding patients was 10 months versus 6 months for nonresponders (46). Hematological toxicity, however, is appreciable, and a high incidence of infectious problems can be expected (46). Regimens containing doxorubicin are most active, and the combination of doxorubicin, bleomycin, and vincristine is relatively well tolerated and frequently used (24). Liposomal daunorubicin, which may target KS cells, is an effective antitumor modality and has less toxicity than when the drug is given as conventional chemotherapy (67,68). In those with cytopenias, the marrow-sparing regimen of vincristine or vinblastine with bleomycin is commonly used (69).
Lipid-based nanoparticle formulations for small molecules and RNA drugs
Published in Expert Opinion on Drug Delivery, 2019
Ludger M. Ickenstein, Patrick Garidel
DaunoXome is a liposomal formulation of daunorubicin, which is structurally closely related to doxorubicin and belongs also to the family of anthracycline antibiotics (Table 2). The liposomal formulation of daunorubicin significantly reduces the systemic elimination of daunorubicin in patients as compared to patients treated with free daunorubicin. The half-life of DaunoXome in patients is approx. 5 h whereas free daunorubicin exhibits a half-life of less than 1 h [93,94]. Because of its altered pharmacokinetic profile, liposomal daunorubicin allows for a longer exposure of the API at the site of action and a greater therapeutic window. In 1999, NeXstar Pharmaceuticals (San Dimas, CA), which developed and produced DaunoXome since 1996, merged with Gilead Sciences Inc. In 2000, Gilead reported product sales of US $ 4.4 million from sales of DaunoXome [95]. In 2006, however, Diatos SA (Paris, France) entered an exclusive licensing agreement with Gilead Sciences for the worldwide development and commercialization rights to DaunoXome.
An overview on the current status of cancer nanomedicines
Published in Current Medical Research and Opinion, 2018
Nasimudeen R. Jabir, Khalid Anwar, Chelapram K. Firoz, Mohammad Oves, Mohammad Amjad Kamal, Shams Tabrez
Liposomal daunorubicin (DaunoXome; DNX) refers to liposome-encapsulated daunorubicin, approved by the US-FDA in 1996 for the treatment of HIV-related Kaposi’s sarcoma24. It is composed of daunorubicin entrapped in small unilamellar vesicles together with distearoyl phosphatidylcholine and cholesterol in a 2:1 molar ratio25. Its anti-cancer mechanism involves inhibition of topoisomerase II, DNA damage and generation of reactive oxygen species (ROS) which results in targeted eradication of leukemic cells26,27. The liposomal encapsulation of daunorubicin significantly reduces cytotoxicity, enhances intracellular accumulation, and controls ROS production and ATP depletion. Because of the liposomal modification, daunorubicin evades dose-dependent toxic effects. In addition, DNX also offer several therapeutic advantages: such as increased plasma drug concentration, improved drug delivery, effective tumor targeting and increased efficacy28,29. Evidence from preclinical studies showed increased tissue concentrations of daunorubicin in tumor tissues30. Liposomal daunorubicin has been reported to have enhanced efficacy in in-vitro and in-vivo models, and in multidrug-resistant cell lines. It has also been suggested as a useful therapy for acute myeloid leukemia (AML) in elderly patients31. It is used as a single agent or in combination with cytarabine in newly diagnosed AML patients and in patients with resistant or relapsed AML32–34. Moreover, DNX has also been reported to increase survival rate when used in combination with photo-immunotherapy in a mouse model35.
Pharmacoeconomic considerations for acute myeloid leukemia pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2022
Monia Marchetti, Luca Albertin, Giulia Limberti, Manuela Canicattì
Liposomal daunorubicin/cytarabine, whose availability was increased, improved the 2-year OS from 12.3% to 27.6% versus standard daunorubicin plus cytarabine formulations (HR 0.69, p = 0.003), thanks to a higher amount of patients for whom allogeneic SCT was accessible. Nevertheless, in the target population – namely patients with AML with myelodysplasia-related changes and therapy-related AML – median OS was improved by less than 4 months [53]. Moreover, the toxicity of liposomal formulations was higher and prolonged aplasia duration was reported.