liposomal cytarabine + temozolomide

The combination of liposomal cytarabine and temozolomide is used primarily for treating central nervous system (CNS) malignancies, particularly those with leptomeningeal involvement. This combination leverages the extended half-life of liposomal cytarabine in the cerebrospinal fluid (CSF) along with temozolomide's ability to cross the blood-brain barrier. ## Formulation and Mechanism Liposomal cytarabine is a suspension of cytosine-arabinoside (Ara-C) encapsulated in multivesicular, lipid-based particles[8]. At body temperature, the biodegradation of the lipid membranes leads to gradual release of Ara-C, ensuring prolonged cytotoxic concentrations in CSF[8]. This formulation significantly extends the half-life of cytarabine in the CSF compared to conventional formulations. Temozolomide is a monofunctional alkylating agent that serves as the first-line chemotherapeutic drug for glioblastoma treatment[7]. Its small size (194 Da) and lipophilicity enhance CNS penetration relative to other alkylating agents, though its concentration in brain tumor tissue is about 20% of plasma levels[9]. When given concurrently with radiation, levels may rise to 35% of plasma concentrations[9]. ## Clinical Applications This combination has shown effectiveness in several CNS malignancies: 1. **Low-grade gliomas with leptomeningeal dissemination**: A case report described complete remission in a 43-year-old male with grade II astrocytoma that had spread to the brain and leptomeninges after 12 months of treatment with this combination[1]. 2. **Primary or secondary central nervous system lymphomas**: The combination has been studied for treating these conditions[2]. 3. **Neoplastic meningitis from breast cancer**: The regimen has shown feasibility and activity in this indication, with intrathecal liposomal cytarabine administered every 2-4 weeks combined with temozolomide 100 mg/m² on days 1-5 of a 7-day cycle[3]. 4. **Medulloblastoma**: Liposomal cytarabine has been used in relapsed medulloblastoma cases, though with varying results[8]. ## Administration The typical administration involves: - **Liposomal cytarabine**: Administered intrathecally every 2-4 weeks[3][8]. In pediatric patients, it has been dosed at 2 mg/kg/dose (maximum 35 mg in children under 13 years, 50 mg in older children)[8]. - **Temozolomide**: Administered orally, often at doses of 75-200 mg/m² depending on the protocol and whether it's given concurrently with radiation[6][9]. - **Prophylactic dexamethasone**: Often administered (0.15 mg/kg/dose, twice daily, orally for five days) to prevent arachnoiditis, a potential side effect of intrathecal liposomal cytarabine[8]. ## Efficacy and Safety The combination appears to be effective while potentially reducing neurotoxicity compared to other regimens[4]. In one case of low-grade oligoastrocytoma with leptomeningeal dissemination, the patient achieved complete remission after 12 months of treatment and remained disease-free for at least 24 months of follow-up[1]. In another case involving a 17-year-old boy with medulloblastoma and diffuse leptomeningeal involvement, the treatment was well-tolerated without transfusion requirements, allowing the patient to maintain regular school attendance and daily activities. The disease remained stable for five months before progression[8]. The combination may be particularly valuable for patients with CNS malignancies that have leptomeningeal involvement, where conventional treatments often have limited efficacy due to poor penetration of the blood-brain barrier and short half-life in the CSF.

Brand names

DepoCyt + Temodar

Other names

ITV DepoCyt + temozolomide