Phase II, multicenter, randomized, open label trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus cytarabine and daunorubicin in patients with untreated AML 60-75 years of age.
ABSTRACT CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this Phase II study newly diagnosed older AML patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (CR+CRi) was the primary endpoint, with event-free survival (EFS) and overall survival (OS) as secondary endpoints. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7%vs.51.2%, P=0.07), meeting predefined criteria for success (P<0.1). Differences in EFS and OS were not statistically significant. A planned analysis of the secondary AML subgroup demonstrated an improved response rate (57.6% vs.31.6%, P=0.06), and prolongation of EFS (HR=0.59, P=0.08) and OS (HR=0.46, P=0.01). Recovery from cytopenias was slower following CPX-351 (median days to ANC≥1000: 36vs.32; Platelets >100K: 37vs.28) with more grade 3-4 infections but without increase in infection-related deaths (3.5%vs.7.3%) or 60-day mortality (4.7% vs.14.6%) indicating acceptable safety. These results suggest clinical benefit with CPX-351, particularly among patients with secondary AML and provide the rationale for a Phase III trial currently underway in newly diagnosed secondary AML patients. This study was registered at Clinicaltrials.gov, identifier: NCT00788892.
Article: Nanomedicine: A pharma perspective[Show abstract] [Hide abstract]
ABSTRACT: Nanotechnology as applied to medicine is not a new field. The first nanomedicines approved for use were developed from research dating back to the 1970s. These liposomal formulations of existing drugs showed improved therapeutic activity and reduced toxicity in the nonclinical model systems. However, these benefits proved more subtle and harder to demonstrate in patients. This fact, combined with the technical challenges in commercial-scale production of nanoparticles, led to only limited investment in nanomedicines by the major pharmaceutical companies. Even so, research on nanomedicines has proceeded apace in academic laboratories and smaller biopharmaceutical companies. New materials and drug combinations have been studied, and targeting moieties added with the aim of improving the therapeutic index. Today many of these new designs are in, or are approaching, clinical testing. It will take only one or two to be successful to change the way pharmaceutical companies view this field of innovative research.Conflict of interest: The authors have declared no conflicts of interest for this article.For further resources related to this article, please visit the WIREs website.Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 08/2014; 7(2). DOI:10.1002/wnan.1288 · 4.24 Impact Factor
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ABSTRACT: Acute myeloid leukemia (AML) is the second most common form of leukemia and the most frequent cause of leukemia-related deaths in the USA. The incidence of AML increases with advancing age and the prognosis for patients with AML worsens substantially with increasing age. Many older patients are ineligible for intensive treatment and require other therapeutic approaches to optimize clinical outcome. To address this treatment gap, novel agents with varying mechanisms of action targeting different cellular processes are currently in development. Hypomethylating agents (azacitidine, decitabine, SGI-110); histone deacetylase inhibitors (vorinostat, pracinostat, panobinostat); FLT3 inhibitors (quizartinib, sorafenib, midostaurin, crenolanib); cytotoxic agents (clofarabine, sapacitabine, vosaroxin), cell cycle inhibitors (barasertib, volasertib, rigosertib) and monoclonal antibodies (gentuzumab ozogamicin, lintuzumab-Ac225) represent some of these promising new treatments. This review provides an overview of novel agents that have either completed or are currently in ongoing phase III trials in patients with previously untreated AML for whom intensive treatment is not an option. Other potential drugs in earlier stages of development will be also addressed in this review.Leukemia accepted article preview online, 21 August 2014; doi:10.1038/leu.2014.244.Leukemia 08/2014; 29(4). DOI:10.1038/leu.2014.244 · 9.38 Impact Factor
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ABSTRACT: Significant advances have been made in the treatment of younger patients with acute myeloid leukemia over the past 3 decades, but prognosis in the elderly has remained dismal, with median survival times of only a few months. Although a small percentage of older patients may be cured by standard chemotherapy, it is clear that several aspects of frontline management require improvement and novel approaches are urgently needed. This review focuses on treatment options currently available to older patients with acute myeloid leukemia, with an emphasis on new therapeutics.Current Opinion in Oncology 08/2014; 26(6). DOI:10.1097/CCO.0000000000000124 · 3.76 Impact Factor