Cytarabine may be administered by intravenous injection or infusion, or subcutaneously. It has been administered intrathecally as a special application.
Thrombophlebitis has occurred at the site of drug injection or infusion in some patients, and rarely patients have noted pain and inflammation at subcutaneous injection sites. In most instances, however, the drug has been well tolerated.
Patients can tolerate higher total doses when they receive the drug by rapid intravenous injection as compared with slow infusion. This phenomenon is related to the drug's rapid inactivation and brief exposure of susceptible normal and neoplastic cells to significant levels after rapid injection. Normal and neoplastic cells seem to respond in somewhat parallel fashion to these different modes of administration and no clear-cut clinical advantage has been demonstrated for either.
Dose regimens are usually at the discretion of the attending physician. Clinical and haematological responses and tolerance vary between patients and a dose which gives optimal therapeutic effect with minimum toxicity should be used.
Normal Adult Dosage, Single Agent Therapy: Doses of up to 200 mg/m2 daily as a continuous intravenous infusion for five days (120 hours) repeated at approximately two weekly intervals have been used. Modification must be made based on results of daily haematological monitoring.
After each five day treatment, drug therapy should be withdrawn to allow for bone marrow recovery.
Dilutions of cytarabine should be made in Glucose 5% or Sodium Chloride 0.9% Intravenous Infusions to concentrations as low as 0.1 mg/mL. In order to reduce any microbiological hazard it is recommended that dilution should be effected immediately prior to use and infusion commenced as soon as practicable after preparation of the admixture. Infusion should be completed within 24 hours of preparation and any residue discarded. Any storage should be between 2°C-8°C, protected from light.
Maintenance of Acute Myelocytic Leukaemia in Adults: Maintenance programs are generally modifications of induction programs. Similar schedules of drug therapy to those used for induction are normally employed. Most programs have a greater interval between courses of therapy during remission maintenance.
Induction and Maintenance of Acute Myelocytic Leukaemia (AML) in Children: Childhood AML has been shown to respond better than adult AML given similar regimes. Where the adult dosage is given in terms of body weight or surface area, the paediatric dosage may be calculated on the same basis, being adjusted on the consideration of such factors as age, body weight or body surface area.
Conditions Requiring Dosage Adjustment: Myelosuppression: The dose of cytarabine should be modified if signs of severe myelosuppression appear, e.g. consideration of discontinuation of the drug if the polymorphonuclear granulocyte count falls below 1 × 109 L or the platelet count falls below 50 × 109 L.
Combination Therapy: Dosage modifications may have to be made when cytarabine is used in combination with other myelosuppressive drugs. Before instituting a programme of combined therapy, the physician should be familiar with the adverse effects, precautions, contraindications and warnings applicable to all the drugs in the programme.
Intrathecal Use in Meningeal Leukaemia: Cytarabine has been used intrathecally in acute leukaemia in doses ranging from 5 mg/m2 to 75 mg/m2 of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment. The dosage schedule is usually governed by the type and severity of central nervous system manifestations and the response to previous therapy.
Cytarabine has been used intrathecally with hydrocortisone sodium succinate and methotrexate, both as prophylaxis in newly diagnosed children with acute lymphocytic leukaemia, as well as in the treatment of meningeal leukaemia. It has been reported that prophylactic triple therapy has prevented late CNS disease and given overall cure and survival rates similar to those seen in patients in whom CNS radiation and intrathecal methotrexate were used as initial CNS prophylaxis. The dose of cytarabine was 30 mg/m2, hydrocortisone sodium succinate 15 mg/m2 and methotrexate 15 mg/m2. The physician should be familiar with this report before initiation of the regimen.
Prophylactic triple therapy following the successful treatment of the acute meningeal episode may be useful. The physician should familiarise himself with the current literature before instituting such a program.