Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis

Jahn, Franziska; Jordan, Karin; Behlendorf, Timo; Globig, Cordula; Schmoll, H.-J.; Müller‐Tidow, Carsten; Jordan, Berit

doi:10.1159/000380913

Cited by 18 publications

(5 citation statements)

References 23 publications

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“…Other groups reported similar response rates (81.8%) in this subgroup of CNS-affected patients and an OS of 11 months[25]. All this highlights the poor prognosis of meningeal lymphomatosis in which new drugs or therapeutic approaches are needed to improve results.…”

Section: Discussionsupporting

confidence: 66%

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience

et al. 2017

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Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20–30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity. Other options are the administration of intrathecal (IT) MTX, cytarabine or liposomal cytarabine (ITLC). Our aim is to analyze the experience of the centers of the Balearic Lymphoma Group (BLG) about the toxicity and efficacy of ITLC in the prophylaxis and therapy of CNS lymphomatosis. We retrospectively reviewed cases from 2005 to 2015 (n = 58) treated with ITLC. Our toxicity results were: 33% headache, 20% neurological deficits, 11% nausea, 9% dizziness, 4% vomiting, 4% fever, 2% transient blindness and 2% photophobia. In the prophylactic cohort (n = 26) with a median follow-up of 55 months (17–81) only 3 CNS relapses (11%) were observed (testicular DLBCL, Burkitt and plasmablastic lymphoma, with a cumulative incidence of 8%, 14% and 20% respectively). In the treatment cohort (n = 32), CSF complete clearance was obtained in 77% cases. Median OS was 6 months (0–16). Death causes were lymphoma progression (19 patients, 79%), treatment toxicity (2 patients) and non-related (3 patients, 12%). Toxicity profile was good especially when concomitant dexamethasone was administered. In the prophylactic cohort the incidence of CNS relapse in DLBCL group was similar to previously reported for HDMTX and much better than IT MTX. A high number of ITLC injections was associated with better rates of CSF clearance, clinical responses, PFS and lower relapses. Survival is still poor in CNS lymphomatosis and new therapeutic approaches are still needed.

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Section: Discussionsupporting

confidence: 66%

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience

et al. 2017

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“…In addition to PEG conjugated lipids, conventional and cationic liposomal-based drugs have also been FDA approved. Liposomal amphotericin B for anti-fungal prophylaxis (Chandrasekar, 2008 ), daunorubicin for the treatment of leukemia and solid tumors (Chang and Yeh, 2012 ), verteporfin to treat macular degeneration (Chang and Yeh, 2012 ), cytarabine or cytosine arabinoside to treat neoplastic meningitis and lymphomatous meningitis (Chang and Yeh, 2012 ; Jahn et al, 2015 ), and morphine sulfate for pain management are currently on the market (Chang and Yeh, 2012 ). Regardless, many of these drugs are still undergoing clinical trials to test their effects of dose escalation and therapeutic efficacy (Chang and Yeh, 2012 ).…”

Section: Clinically Approved Liposomal-based Therapeuticsmentioning

confidence: 99%

Advances and Challenges of Liposome Assisted Drug Delivery

et al. 2015

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The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

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“…Several anticancer nanomedicines have been approved for clinical use in cancer patients in the past few decades. These products include two doxorubicin liposomal nanoformulations (Doxil − and Myocet , ), six paclitaxel nanomedicines (Abraxane [albumin nanoparticle of paclitaxel], − Genexol-PM [polymeric nanoparticle of paclitaxel], Lipusu [liposomal paclitaxel], PICN [liposomal paclitaxel nanosuspension], , Paclical or Apealea [paclitaxel micellar], , and DP107 [paclitaxel lipid nanoparticle]), one daunorubicin liposome nanoformulation (DaunoXome), , one vincristine liposomal nanoformulation (Margibo), , one mifamurtide liposomal nanoformulation (MEPACT), one irinotecan liposomal formulation (Onivyde), , one Cytarabine liposome injection (DepoCyt), , and one liposomal daunorubicin and cytarabine (Vyxeos). ,,, …”

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confidence: 99%