Skip to main content
Top
Published in: Journal of Neuro-Oncology 3/2013

01-12-2013 | Clinical Study

Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa

Authors: A. Comte, W. Jdid, M. N. Guilhaume, I. Kriegel, S. Piperno-Neumann, V. Dieras, T. Dorval, J. Y. Pierga, P. H. Cottu, L. Mignot, F. C. Bidard

Published in: Journal of Neuro-Oncology | Issue 3/2013

Login to get access

Abstract

Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1–50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6–7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50–5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.
Literature
1.
go back to reference DeAngelis LM (1998) Current diagnosis and treatment of leptomeningeal metastasis. J Neurooncol 38(2–3):245–252PubMedCrossRef DeAngelis LM (1998) Current diagnosis and treatment of leptomeningeal metastasis. J Neurooncol 38(2–3):245–252PubMedCrossRef
3.
go back to reference Wasserstrom WR, Glass JP, Posner JB (1982) Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 49(4):759–772PubMedCrossRef Wasserstrom WR, Glass JP, Posner JB (1982) Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 49(4):759–772PubMedCrossRef
5.
go back to reference Beauchesne P (2010) Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours. Lancet Oncol 11(9):871–879PubMedCrossRef Beauchesne P (2010) Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours. Lancet Oncol 11(9):871–879PubMedCrossRef
6.
go back to reference Shapiro WR, Johanson CE, Boogerd W (2009) Treatment modalities for leptomeningeal metastases. Semin Oncol 36(4 Suppl 2):S46–S54PubMedCrossRef Shapiro WR, Johanson CE, Boogerd W (2009) Treatment modalities for leptomeningeal metastases. Semin Oncol 36(4 Suppl 2):S46–S54PubMedCrossRef
7.
go back to reference 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(10):1655–1662PubMed 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(10):1655–1662PubMed
8.
go back to reference Glantz MJ, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ, Maria B, LaFollette S, Schumann GB, Cole BF, Howell SB (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(11):3394–3402PubMed Glantz MJ, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ, Maria B, LaFollette S, Schumann GB, Cole BF, Howell SB (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(11):3394–3402PubMed
9.
go back to reference Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR (1982) Treatment for meningeal carcinomatosis in breast cancer. Cancer 50(2):219–222PubMedCrossRef Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR (1982) Treatment for meningeal carcinomatosis in breast cancer. Cancer 50(2):219–222PubMedCrossRef
10.
go back to reference Ongerboer de Visser BW, Somers R, Nooyen WH, van Heerde P, Hart AA, McVie JG (1983) Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Neurology 33(12):1565–1572PubMedCrossRef Ongerboer de Visser BW, Somers R, Nooyen WH, van Heerde P, Hart AA, McVie JG (1983) Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Neurology 33(12):1565–1572PubMedCrossRef
11.
go back to reference Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, Beuzeboc P, Dorval T, Pouillart P (1996) Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer 77(7):1315–1323PubMedCrossRef Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, Beuzeboc P, Dorval T, Pouillart P (1996) Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer 77(7):1315–1323PubMedCrossRef
12.
go back to reference Chamberlain MC (2012) Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for the treatment of leptomeningeal metastases: a retrospective case series. J Neurooncol 109(1):143–148 Chamberlain MC (2012) Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for the treatment of leptomeningeal metastases: a retrospective case series. J Neurooncol 109(1):143–148
13.
go back to reference Bleyer WA, Drake JC, Chabner BA (1973) Neurotoxicity and elevated cerebrospinal-fluid methotrexate concentration in meningeal leukemia. N Engl J Med 289(15):770–773PubMedCrossRef Bleyer WA, Drake JC, Chabner BA (1973) Neurotoxicity and elevated cerebrospinal-fluid methotrexate concentration in meningeal leukemia. N Engl J Med 289(15):770–773PubMedCrossRef
14.
go back to reference Gutin PH, Levi JA, Wiernik PH, Walker MD (1977) Treatment of malignant meningeal disease with intrathecal thioTEPA: a phase II study. Cancer Treat Rep 61(5):885–887PubMed Gutin PH, Levi JA, Wiernik PH, Walker MD (1977) Treatment of malignant meningeal disease with intrathecal thioTEPA: a phase II study. Cancer Treat Rep 61(5):885–887PubMed
15.
go back to reference Gutin PH, Weiss HD, Wiernik PH, Walker MD (1976) Intrathecal N,N′,N″-triethylenethiophosphoramide [thio-TEPA (NSC 6396)] in the treatment of malignant meningeal disease: phase I-II study. Cancer 38(4):1471–1475PubMedCrossRef Gutin PH, Weiss HD, Wiernik PH, Walker MD (1976) Intrathecal N,N′,N-triethylenethiophosphoramide [thio-TEPA (NSC 6396)] in the treatment of malignant meningeal disease: phase I-II study. Cancer 38(4):1471–1475PubMedCrossRef
16.
go back to reference Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS (1993) Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol 11(3):561–569PubMed Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS (1993) Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol 11(3):561–569PubMed
17.
go back to reference Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, Laurence V, Livartowski A, Mignot L, Dieras V (2010) Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21(11):2183–2187PubMedCrossRef Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, Laurence V, Livartowski A, Mignot L, Dieras V (2010) Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21(11):2183–2187PubMedCrossRef
18.
go back to reference Giannone L, Greco FA, Hainsworth JD (1986) Combination intraventricular chemotherapy for meningeal neoplasia. J Clin Oncol 4(1):68–73PubMed Giannone L, Greco FA, Hainsworth JD (1986) Combination intraventricular chemotherapy for meningeal neoplasia. J Clin Oncol 4(1):68–73PubMed
19.
go back to reference Bidard FC, Lossignol D, Larsimont D, Piccart M, Awada A (2011) Validation of the Institut Curie simplified prognostic score for breast cancer meningeal carcinomatosis. Ann Oncol 22(2):480–482PubMedCrossRef Bidard FC, Lossignol D, Larsimont D, Piccart M, Awada A (2011) Validation of the Institut Curie simplified prognostic score for breast cancer meningeal carcinomatosis. Ann Oncol 22(2):480–482PubMedCrossRef
Metadata
Title
Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa
Authors
A. Comte
W. Jdid
M. N. Guilhaume
I. Kriegel
S. Piperno-Neumann
V. Dieras
T. Dorval
J. Y. Pierga
P. H. Cottu
L. Mignot
F. C. Bidard
Publication date
01-12-2013
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-013-1244-x

Other articles of this Issue 3/2013

Journal of Neuro-Oncology 3/2013 Go to the issue