Abstract
Interesting neurological and cytological response rates after intrathecal (i.t) liposomal cytarabine have been observed in patients with leptomeningeal carcinomatosis (LMC) from solid tumors. However, the potential use of those responses as early predictors of time-to-progression (TTP) and overall survival (OS) is unexplored. 27 consecutive patients with LMC treated with 50 mg i.t liposomal cytarabine under compassionate drug use were retrospectively studied. All patients received i.t treatment every 2 weeks during induction and every 4 weeks during maintenance periods. Neurological and cytological responses were assessed before every liposomal cytarabine cycle. Most of the patients were female (17/27) diagnosed with breast cancer (15/27). A complete neurological response was seen among 11 % of the patients; partial response in 22 % of the patients; stable disease in 30 % of the patients and progressive disease in 37 % of them. Cytological assessment was available in 11/27 patients showing a 26 % complete response rate. The median time to neurological and cytological response was 15 days and 14 days, respectively. Patients showing a combined neurological and cytological response showed a significantly longer median TTP (122 vs. 3 days; p = 0.001) and OS (141 vs. 3 days; p = 0.002) compared to those showing both neurological and cytological progression. No grade 4 toxicities were recorded. According to these preliminary results, early neurological and cytological responses may be further studied as early predictors of TTP and OS in patients receiving i.t liposomal cytarabine for LMC.
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References
Chamberlain MC (2012) Neoplastic meningitis and metastatic epidural spinal cord compression. Hematol Oncol Clin North Am 26:917–931
Subira D, Serrano C, Castanon S et al (2012) Role of flow cytometry immunophenotyping in the diagnosis of leptomeningeal carcinomatosis. Neuro Oncol 14:43–52
Thomas JE, Falls E, Velasco ME, Zaher A (2000) Diagnostic value of immunocytochemistry in leptomeningeal tumor dissemination. Arch Pathol Lab Med 124:759–761
Bruna J, Gonzalez L, Miro J et al (2009) Leptomeningeal carcinomatosis: prognostic implications of clinical and cerebrospinal fluid features. Cancer 115:381–389
Pentheroudakis G, Pavlidis N (2005) Management of leptomeningeal malignancy. Expert Opin Pharmacother 6:1115–1125
Hitchins RN, Bell DR, Woods RL, Levi JA (1987) A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5:1655–1662
Morris PG, Reiner AS, Szenberg OR et al (2012) Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 7:382–385
Beauchesne P (2010) Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours. Lancet Oncol 11:871–879
Phuphanich S, Maria B, Braeckman R, Chamberlain M (2007) A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study. J Neurooncol 81:201–208
Jaeckle KA, Batchelor T, O’Day SJ et al (2002) An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol 57:231–239
Glantz MJ, Jaeckle KA, Chamberlain MC et al (1999) A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 5:3394–3402
Navajas A, Lassaletta A, Morales A, López-Ibor B, Sábado C, Moscardó C, Mateos E, Molina J, Sagaseta M, Sastre A (2012) Efficacy and safety of liposomal cytarabine in children with primary CNS tumours with leptomeningeal involvement. Clin Transl Oncol 14(4):280–286
ftp://ftp1.nci.nih.gov/pub/cacore/EVS/CTCAE/Archive/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf
Rudnicka H, Niwińska A, Murawska M (2007) Breast cancer leptomeningeal metastasis: the role of multimodality treatment. J Neurooncol 84(1):57–62
Park JH, Kim YJ, Lee JO, Lee KW, Kim JH, Bang SM, Chung JH, Kim JS, Lee JS (2012) Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era. Lung Cancer 76(3):387–392
Chamberlain MC, Johnston SK, Glantz MJ (2009) Neoplastic meningitis-related prognostic significance of the Karnofsky performance status. Arch Neurol 66:74–78
Kim DY, Lee KW, Yun T et al (2003) Comparison of intrathecal chemotherapy for leptomeningeal carcinomatosis of a solid tumor: methotrexate alone versus methotrexate in combination with cytosine arabinoside and hydrocortisone. Jpn J Clin Oncol 33:608–612
Le Rhun E, Taillibert S, Zairi F, Kotecki N, Devos P, Mailliez A, Servent V, Vanlemmens L, Vennin P, Boulanger T, Baranzelli MC, André C, Marliot G, Cazin JL, Dubois F, Assaker R, Bonneterre J, Chamberlain MC (2013) A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol 113(1):83–92
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The authors wish to thank Mr. Anthony Stevens for editorial assistance.
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Fusco, J.P., Castañón, E., Carranza, O.E. et al. Neurological and cytological response as potential early predictors of time-to-progression and overall survival in patients with leptomeningeal carcinomatosis treated with intrathecal liposomal cytarabine: a retrospective cohort study. J Neurooncol 115, 429–435 (2013). https://doi.org/10.1007/s11060-013-1241-0
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DOI: https://doi.org/10.1007/s11060-013-1241-0