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Chamberlain MC. J Neurooncol 2016;126:545–550

 

Cytarabine 3000 mg/m2 per dose; administer intravenously in 100–1000 mL 0.9% sodium chloride injection or 5% dextrose injection over 3 hours, every 12 hours for 4 doses (2 doses/day) on days 1 and 2, every 28 days, until disease progression (total dosage/cycle = 12,000 mg/m2)

  • Note:

    • Patients with renal dysfunction and/or elderly patients are at increased risk of high-dose cytarabine-induced cerebellar toxicity; consider initiating treatment at a reduced dose. Dose reduction recommendations vary; one commonly cited reference (Kintzel PE, Dorr RT. Cancer Treat Rev 1995;21:33–64) suggests:

      • Creatinine clearance 46–60 mL/min: Reduce dose to 1800 mg/m2 per dose

      • Creatinine clearance 31–45 mL/min: Reduce dose to 1500 mg/m2 per dose

      • Creatinine clearance <30 mL/min: Consider use of alternative drug

 

Supportive Care

Antiemetic prophylaxis

Emetogenic potential is MODERATE

See Chapter 39 for antiemetic recommendations

 

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is indicated with one of the following:

Filgrastim (G-CSF) 5 mcg/kg/day, by subcutaneous injection, or

Pegfilgrastim (pegylated filgrastim) 6 mg/0.6 mL, by subcutaneous injection for 1 dose

  • Begin use from 24–72 hours after myelosuppressive chemotherapy is completed

  • Continue daily filgrastim use until ANC ≥5000/mm3 after the leukocyte nadir

  • Discontinue daily filgrastim use at least 24 hours before administering myelosuppressive treatment. Do not administer pegfilgrastim within 14 days before administering myelosuppressive treatment

See Chapter 43 for more information

 

Antimicrobial prophylaxis

Risk of fever and neutropenia is HIGH

  Antimicrobial primary prophylaxis is recommended:

  • Antibacterial—consider fluoroquinolone prophylaxis during periods of neutropenia

  • Antifungal—fluconazole is recommended during periods of neutropenia

  • Antiviral—antiherpes antivirals (eg, acyclovir, famciclovir, valacyclovir)

See Chapter 47 for more information

 

Keratitis prophylaxis

Steroid ophthalmic drops (prednisolone 1% or dexamethasone 0.1%); administer 2 drops by intraocular instillation into each eye every 6 hours starting prior to the first cytarabine dose and continuing until 48 hours after high-dose cytarabine is completed

Patient Population Studied

A retrospective review was performed for 14 patients with recurrent primary central nervous system lymphoma (PCNSL) after having failed first-line treatment (high-dose methotrexate plus rituximab) and second-line therapy (first salvage; temozolomide in 5 patients, high-dose methotrexate plus rituximab in 5 patients, and procarbazine plus lomustine plus vincristine in 4 patients). All patients received high-dose cytarabine (3 g/m2 over a 3 hour infusion) every 12 hours for 4 treatments and then, 12 hours after the final dose of cytarabine, pegfilgrastim (6 mg).

Efficacy (N = 14)

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Efficacy (N = 14)

Median progression-free survival

3 months

6-month progression-free survival

0%

Median overall survival

12 months

Therapy Monitoring

  1. CBC with differential and platelet counts and comprehensive metabolic panel daily during chemotherapy

  2. Outpatient monitoring post-chemotherapy: CBC with differential, platelets, and comprehensive metabolic panel, 2–3 times weekly until counts recover

  3. Monitor for signs of cerebellar toxicity (nystagmus, dysmetria, and ataxia) before each dose of cytarabine

  4. Patients who receive high-dose cytarabine need to be closely monitored for changes in renal function. Renal dysfunction is highly correlated with an increased risk of cerebellar toxicity

  5. Response assessment: Contrast-enhanced MRI of the brain prior to each cycle of chemotherapy

Treatment Modifications

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Treatment Modifications

HIGH-DOSE CYTARABINE

Adverse Event

Treatment Modification

Fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise, 6–12 hours following drug administration (cytarabine or Ara-C syndrome).

Corticosteroids are beneficial in treating or preventing this syndrome. If the symptoms are deemed treatable, continue therapy with cytarabine and pretreat with corticosteroids

Neurologic (cerebellar) toxicity

Hold cytarabine. Patients who develop CNS symptoms should not receive subsequent high-dose cytarabine.

ANC <1000/mm3 or platelet count <50,000/mm3

Consider suspending or modifying doses/schedule.

Note: ANC and platelet count may continue to fall after the drug is stopped and reach lowest values after drug-free intervals of 12–24 days. When definite signs of marrow recovery appear, restart therapy

Adverse Events (N = 14)

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Adverse Events (N = 14)

Grade (%)

Grade 1/2

Grade 3

Grade 4

Neutropenia

43

36

21

Anemia

29

57

14

Lymphopenia

43

43

14

Mucositis

43

43

14

Thrombocytopenia

21

71

7

Fatigue

43

50

7

Neutropenic fever

14

29

7

Conjunctivitis

36

21

0

Nausea

43

14

0

Infection without neutropenia

7

14

0

Encephalopathy

14

7

0

According to the National Cancer Institute Common Terminology Criteria for Adverse Events

Note: No treatment-related deaths were recorded and no patient discontinued therapy because of toxicity.

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