Randomized Trial of a Slow-Release Versus a Standard Formulation of Cytarabine for the Intrathecal Treatment of Lymphomatous Meningitis

Glantz, Michael; LaFollette, Suzanne; Jaeckle, Kurt A.; Shapiro, William R.; Swinnen, Lode J.; Rozental, Jack R.; Phuphanich, Surasak; Rogers, Lisa; Gutheil, John; Batchelor, Tracy T.; Lyter, David W.; Chamberlain, Marc C.; Maria, Bernard L.; Schiffer, Charles A.; Bashir, Rifaat; Thomas, David M.; Cowens, Wayne; Howell, Stephen B.

doi:10.1200/jco.1999.17.10.3110

Cited by 372 publications

(239 citation statements)

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“…Liposomal cytarabine has been used only in the therapeutic setting both for HIV 31 and in the general population. [24][25][26][27][28][29][30] In particular, the only study of the treatment of lymphomatous meningitis in 5 patients with HIV-NHL showed a 60% CR rate. 31 There is only limited experience in the prophylactic setting in patients with aggressive lymphoma in the general population, whereas some data have been published in patients with acute lymphocytic or myeloid leukemia.…”

Section: Discussionmentioning

confidence: 99%

“…Liposomal cytarabine was administered at the standard dose of 50 mg [24][25][26][27][28][29][30][31] by lumbar sac injection on Day 1 of the systemic treatment. The use of intrathecal steroids was not allowed.…”

Section: Treatmentmentioning

confidence: 99%

“…16,17,20 Recently, a liposomal formulation of cytarabine (DepoCyte) has shown similar activity of free cytarabine, with a lower toxicity profile and a more convenient dosing regimen in the treatment of both lymphomatous meningitis and meningitis from solid tumors. [24][25][26][27][28][29][30] Up to now, there are no data on the efficacy and safety of liposomal cytarabine in the prophylaxis of CSF recurrence or progression in HIV-positive patients, although it has been used in the therapeutic setting. 31 With the aim of evaluating the feasibility and activity of liposomal cytarabine in the setting of prophylaxis in HIV-related NHL, from May 2006 to December 2008 we started a phase 2 prospective study at the National Cancer Institute in Aviano, Italy.…”

mentioning

confidence: 99%

“…The incidence of headache in our study was similar to that reported in all published studies of liposomal cytarabine in the treatment of lymphomatous meningitis. [24][25][26][27][28][29][30] The other side effects were negligible. Up to now, with a median follow-up of 10.5 months, only 1 (3%) patient with Burkitt lymphoma, who did not receive all the planned injections, has developed disease recurrence in the CSF after 12 months from the end of the treatment.…”

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confidence: 99%

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Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

Spina

Chimienti

Martellotta

et al. 2010

Cancer

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BACKGROUND:Patients with aggressive non-Hodgkin lymphoma (NHL) develop central nervous system (CNS) progression or recurrence during the course of their disease. Patients with human immunodeficiency virus (HIV)-NHL often develop CNS progression despite the use of prophylaxis. Liposomal cytarabine (DepoCyte) has shown activity in lymphomatous meningitis, but there are limited data for prophylaxis. METHODS: Between May 2006 and December 2008, a phase 2 study of intrathecal liposomal cytarabine was performed at the dose of 50 mg in 30 patients with HIV-NHL, with the aim of evaluating feasibility and activity for prophylaxis. RESULTS: Liposomal cytarabine was well tolerated, with headache grade I to III being the most frequent side effect in 40% of patients. With a median followup of 10.5 months, only 1 (3%) patient developed a combined systemic and meningeal recurrence. The use of liposomal cytarabine allowed significant reduction of the number of lumbar injections in comparison to the standard schedules (around 50%), improving the quality of life of patients and reducing the professional exposure risk. CONCLUSIONS: In this first study on prophylaxis of lymphomatous meningitis in HIV-NHL, liposomal cytarabine seems safe and active; it reduces by approximately 50% the number of lumbar punctures, and exposure risk for health staff as well.

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Section: Discussionmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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confidence: 99%

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Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

Spina

Chimienti

Martellotta

et al. 2010

Cancer

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“…Methotrexate (MTX) and liposomal cytarabine are the most frequently used agents for IC of LM from solid tumors. Liposomal cytarabine showed a better neurological progression‐free survival and a better impact on the quality of life 15, 16, 17. Nevertheless, all of the included subjects were suffered from lymphoma in these studies except one17 including patients with breast cancer, lung cancer, melanoma, primary brain tumor and other conditions.…”

mentioning

confidence: 98%

Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single‐arm study

Pan

Yang

et al. 2016

Intl Journal of Cancer

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The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved‐field radiotherapy (IF‐RT) for treating LM from solid tumors with adverse prognostic factors. Fifty‐nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5–15 mg and dexamethasone 5 mg, weekly) and IF‐RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1–3 times) was given before concurrent therapy. Thirty‐eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20–70). Fifty‐one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1‐year‐survival rate was 21.3%. Treatment‐related adverse events mainly included acute meningitis, chronic‐delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III–V toxic reactions. We concluded that IC combined with concomitant IF‐RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective clinical study, the authors combined intrathecal methotrexate with involved‐field radiotherapy in a concomitant regimen, showing that the approach can potentially improve quality of life for patients with adverse prognostic factors. Concurrent radiotherapy‐bolstered IC by contributing to prolonged remission of neurological symptoms and increasing OS. The findings suggest that the concomitant regimen could be an optimal treatment option for LM.

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Commentary Regarding Neoplastic Meningitis Secondary to Multiple Myeloma

Chamberlain

2005

Arch Neurol

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Randomized Trial of a Slow-Release Versus a Standard Formulation of Cytarabine for the Intrathecal Treatment of Lymphomatous Meningitis

Abstract: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.

Cited by 372 publications

References 15 publications

Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single‐arm study

Commentary Regarding Neoplastic Meningitis Secondary to Multiple Myeloma

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