title: Intrathecal chemotherapy with antineoplastic agents in children.
abstract: Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. Intrathecal MTX administered sequentially with systemic high dose MTX infusion prolongs therapeutic cerebral spinal fluid (CSF) levels of the drug. Prolonged therapeutic CSF levels can also be achieved by giving repeated small intrathecal doses of MTX over an extended period in selected patients, with an implanted Ommaya reservoir. In the CSF, the metabolic inactivation of Ara-C is significantly lower than in plasma with a CSF clearance similar to the rate of CSF bulk flow. A slow-release formulation of Ara-C may be given intrathecally, resulting in a prolonged cytotoxic concentration in the CSF. CNS relapse and neurotoxicity in patients with acute lymphoblastic leukaemia, especially younger children, may be reduced by using age-related dosing of intrathecal MTX and Ara-C. Hydrocortisone is used in combination with MTX and Ara-C for so-called 'triple intrathecal chemotherapy' in the treatment of meningeal leukaemia. Intrathecal thiotepa does not appear to be advantageous over systemic administration in patients with brain and meningeal leukaemia. Monoclonal antibodies, reactive with tumour-associated antigens, can be used as delivery systems for chemotherapeutic agents and radionuclides. However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.
authors.affiliation: Division of Paediatric Oncology, Catholic University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ruggiero
authors.forename: V
authors.initials: V
authors.lastname: Conter
authors.forename: M
authors.initials: M
authors.lastname: Milani
authors.forename: E
authors.initials: E
authors.lastname: Biagi
authors.forename: I
authors.initials: I
authors.lastname: Lazzareschi
authors.forename: P
authors.initials: P
authors.lastname: Sparano
authors.forename: R
authors.initials: R
authors.lastname: Riccardi
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D002555:Cerebrospinal Fluid / Q000187:drug effects; D002648:Child; D003561:Cytarabine / Q000627:therapeutic use; D006801:Humans; D007278:Injections, Spinal; D008223:Lymphoma / Q000188:drug therapy*; D008527:Medulloblastoma / Q000188:drug therapy*; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013852:Thiotepa / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D003561:Cytarabine; D013852:Thiotepa; D015122:Mercaptopurine; D008727:Methotrexate