Intrathecal liposomal cytarabine in relapsed or refractory infant and pediatric leukemias: the Children's Hospital of Philadelphia experience and review of the literature.
ABSTRACT Intrathecal chemotherapy is integral to curing childhood leukemia; however, bioavailability is limited by the blood-brain barrier. Recently FDA-approved, intrathecal liposomal cytarabine (ITlipAC) increases drug concentration over time with fewer invasive procedures. We present a series of 4 children, including 2 infants, with relapsed central nervous system leukemia who went into remission using ITlipAC, with a review of the literature reporting ITlipAC use in children with relapsed leukemia. Drug-attributable side effects were observed more frequently in children with preexisting neurologic conditions and with adult dosing. Combined with other pediatric reports, our experience supports the efficacy of ITlipAC in pediatric and infant leukemic meningitis.
SourceAvailable from: Alejandro Sosnik[Show abstract] [Hide abstract]
ABSTRACT: Nanotechnology has become a key tool to overcome the main (bio)pharmaceutical drawbacks of drugs and to enable their passive or active targeting to specific cells and tissues. Pediatric therapies usually rely on the previous clinical experience in adults. However, there exists scientific evidence that drug pharmacokinetics and pharmacodynamics in children differ from those in adults. For example, the interaction of specific drugs with their target receptors undergoes changes over the maturation of the different organs and systems. A similar phenomenon is observed for toxicity and adverse effects. Thus, it is clear that the treatment of disease in children cannot be simplified to the direct adjustment of the dose to the body weight/surface. In this context, the implementation of innovative technologies (e.g., nanotechnology) in the pediatric population becomes extremely challenging. The present article overviews the different attempts to use nanotechnology to treat diseases in the pediatric population. Due to the relevance, though limited available literature on the matter, we initially describe from preliminary in vitro studies to preclinical and clinical trials aiming to treat pediatric infectious diseases and pediatric solid tumors by means of nanotechnology. Then, the perspectives of pediatric nanomedicine are discussed.Advanced drug delivery reviews 05/2014; 73. DOI:10.1016/j.addr.2014.05.004 · 12.71 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Classical chemotherapeutic agents such as mitotic inhibitors (spindle poisons), alkylating agents, antimetabolites, topoisomerase inhibitors, and anthracenediones (anthracyclines) inhibit DNA synthesis and mitosis, thereby killing or impeding the proliferation of rapidly dividing cells. During the last decade, targeted therapy has gained advantage over conventional treatment regimens, as it is more effective against cancer and also much less harmful to normal cells, thus minimizing the side-effects of chemotherapy. This type of treatment blocks the proliferation of cancer cells by inhibiting the function of specific targeted molecules needed for tumor growth and metastasis. Targeted therapy agents include monoclonal antibodies and small-molecule inhibitors, which most commonly target receptor and/or non-receptor tyrosine kinases. Most members of the BCL2 apoptosis-related family regulate cellular fate as a response to antineoplastic agents. Modulations at the mRNA and protein levels of these genes are usually associated with sensitivity or resistance of various types of cancer cells to chemotherapeutic drugs. Moreover, alterations in expression of BCL2-family members, induced by anticancer drug treatment, can trigger or simply facilitate apoptosis. In this review, we summarize information about changes in apoptosis-related gene expression caused directly or indirectly by antineoplastic agents, as well as about the impact of BCL2-family members on the chemosensitivity or chemoresistance of cancer cells.Anti-cancer agents in medicinal chemistry 06/2013; DOI:10.2174/18715206113139990091 · 2.94 Impact Factor