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Published in: Journal of Neuro-Oncology 1/2013

01-10-2013 | Clinical Study

Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma

Authors: Jun-Ping Zhang, Eudocia Q. Lee, Lakshmi Nayak, Lisa Doherty, Santosh Kesari, Alona Muzikansky, Andrew D. Norden, Huichao Chen, Patrick Y. Wen, Jan Drappatz

Published in: Journal of Neuro-Oncology | Issue 1/2013

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Abstract

There is currently no standard therapy for recurrent or chemotherapy-refractory central nervous system lymphoma (CNSL). Pemetrexed has been reported to have activity in patients with primary CNSL (PCNSL). The use of pemetrexed in secondary CNS lymphoma (SCNSL) has not previously been reported. Here we retrospectively review the outcomes and toxicities of standard and modified doses of pemetrexed as salvage therapy in 18 PCNSL and 12 SCNSL patients. The overall response rate for PCNSL patients was 64.7 %, all of whom achieved a complete response (CR). The median progression-free survival (PFS) was 5.8 months. For the SCNSL patients, RR was 58.3 % with 2 CR (16.7 %); the median PFS was 2.5 months. Grade ≥3 adverse events included leukopenia in 5 patients (16.7 %), neutropenia in 1 patient (3.3 %), and fatigue in 3 patients (10.0 %). 3 patients died while on treatment, 2 due to infections and 1 due to pulmonary embolism. Our results indicate that pemetrexed has activity as salvage therapy in recurrent PCNSL, even with modified dosing, but outcomes trend towards less favorable in SCNSL.
Literature
1.
go back to reference Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI (2009) Natural history of CNS relapse in patients with aggressive non-Hodgkin’s lymphoma: a 20-year follow-up analysis of SWOG 8516: the Southwest Oncology Group. J Clin Oncol 27:114–119PubMedCrossRef Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI (2009) Natural history of CNS relapse in patients with aggressive non-Hodgkin’s lymphoma: a 20-year follow-up analysis of SWOG 8516: the Southwest Oncology Group. J Clin Oncol 27:114–119PubMedCrossRef
2.
3.
go back to reference Arellano-Rodrigo E, Lopez-Guillermo A, Bessell EM, Nomdedeu B, Montserrat E, Graus F (2003) Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma. Eur J Haematol 70:219–224PubMedCrossRef Arellano-Rodrigo E, Lopez-Guillermo A, Bessell EM, Nomdedeu B, Montserrat E, Graus F (2003) Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma. Eur J Haematol 70:219–224PubMedCrossRef
4.
go back to reference Plotkin SR, Betensky RA, Hochberg FH, Grossman SA, Lesser GJ, Nabors LB, Chon B, Batchelor TT (2004) Treatment of relapsed central nervous system lymphoma with high-dose methotrexate. Clin Cancer Res 10:5643–5646PubMedCrossRef Plotkin SR, Betensky RA, Hochberg FH, Grossman SA, Lesser GJ, Nabors LB, Chon B, Batchelor TT (2004) Treatment of relapsed central nervous system lymphoma with high-dose methotrexate. Clin Cancer Res 10:5643–5646PubMedCrossRef
5.
go back to reference Makino K, Nakamura H, Hide T, Kuratsu J (2012) Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status. J Neurooncol 106:155–160PubMedCrossRef Makino K, Nakamura H, Hide T, Kuratsu J (2012) Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status. J Neurooncol 106:155–160PubMedCrossRef
6.
go back to reference Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M, Bordonaro R, Ilariucci F, Faedi M, Corazzelli G, Manno P, Franceschi E, Pace A, Candela M, Abbadessa A, Stelitano C, Latte G, Ferreri AJ (2007) Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer 96:864–867PubMedCrossRef Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M, Bordonaro R, Ilariucci F, Faedi M, Corazzelli G, Manno P, Franceschi E, Pace A, Candela M, Abbadessa A, Stelitano C, Latte G, Ferreri AJ (2007) Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer 96:864–867PubMedCrossRef
7.
go back to reference Enting RH, Demopoulos A, DeAngelis LM, Abrey LE (2004) Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 63:901–903PubMedCrossRef Enting RH, Demopoulos A, DeAngelis LM, Abrey LE (2004) Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 63:901–903PubMedCrossRef
8.
go back to reference Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A (2012) Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma 19(11):1501–1505 Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A (2012) Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma 19(11):1501–1505
9.
go back to reference Fischer L, Thiel E, Klasen HA, Birkmann J, Jahnke K, Martus P, Korfel A (2006) Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 17:1141–1145PubMedCrossRef Fischer L, Thiel E, Klasen HA, Birkmann J, Jahnke K, Martus P, Korfel A (2006) Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 17:1141–1145PubMedCrossRef
10.
go back to reference Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T (2008) Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol 86:211–215PubMedCrossRef Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T (2008) Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol 86:211–215PubMedCrossRef
11.
go back to reference Raizer JJ, Rademaker A, Evens AM, Rice L, Schwartz M, Chandler JP, Getch CC, Tellez C, Grimm SA (2012) Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma. Cancer 118:3743–3748PubMedCrossRef Raizer JJ, Rademaker A, Evens AM, Rice L, Schwartz M, Chandler JP, Getch CC, Tellez C, Grimm SA (2012) Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma. Cancer 118:3743–3748PubMedCrossRef
12.
go back to reference Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V (2008) Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 26:2512–2518PubMedCrossRef Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V (2008) Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 26:2512–2518PubMedCrossRef
13.
go back to reference Hottinger AF, DeAngelis LM, Yahalom J, Abrey LE (2007) Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology 69:1178–1182PubMedCrossRef Hottinger AF, DeAngelis LM, Yahalom J, Abrey LE (2007) Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology 69:1178–1182PubMedCrossRef
14.
go back to reference Macdonald DR, Cascino TL, Schold SC Jr (1990) Cairncross JG: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed Macdonald DR, Cascino TL, Schold SC Jr (1990) Cairncross JG: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed
15.
go back to reference Herrlinger U, Brugger W, Bamberg M, Kuker W, Dichgans J, Weller M (2000) PCV salvage chemotherapy for recurrent primary CNS lymphoma. Neurology 54:1707–1708PubMedCrossRef Herrlinger U, Brugger W, Bamberg M, Kuker W, Dichgans J, Weller M (2000) PCV salvage chemotherapy for recurrent primary CNS lymphoma. Neurology 54:1707–1708PubMedCrossRef
16.
go back to reference Reni M, Ferreri AJ, Landoni C, Villa E (2000) Salvage therapy with temozolomide in an immunocompetent patient with primary brain lymphoma. J Natl Cancer Inst 92:575–576PubMedCrossRef Reni M, Ferreri AJ, Landoni C, Villa E (2000) Salvage therapy with temozolomide in an immunocompetent patient with primary brain lymphoma. J Natl Cancer Inst 92:575–576PubMedCrossRef
17.
go back to reference Wong SF, Gan HK, Cher L (2012) A single centre study of the treatment of relapsed primary central nervous system lymphoma (PCNSL) with single agent temozolomide. J Clin Neurosci 19:1501–1505PubMedCrossRef Wong SF, Gan HK, Cher L (2012) A single centre study of the treatment of relapsed primary central nervous system lymphoma (PCNSL) with single agent temozolomide. J Clin Neurosci 19:1501–1505PubMedCrossRef
18.
go back to reference Wong ET (2005) Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 64:934PubMedCrossRef Wong ET (2005) Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 64:934PubMedCrossRef
19.
go back to reference Batchelor TT, Grossman SA, Mikkelsen T, Ye X, Desideri S, Lesser GJ (2011) Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology 76:929–930PubMedCrossRef Batchelor TT, Grossman SA, Mikkelsen T, Ye X, Desideri S, Lesser GJ (2011) Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology 76:929–930PubMedCrossRef
20.
go back to reference Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A (2013) Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma 54:58–61PubMedCrossRef Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A (2013) Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma 54:58–61PubMedCrossRef
Metadata
Title
Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma
Authors
Jun-Ping Zhang
Eudocia Q. Lee
Lakshmi Nayak
Lisa Doherty
Santosh Kesari
Alona Muzikansky
Andrew D. Norden
Huichao Chen
Patrick Y. Wen
Jan Drappatz
Publication date
01-10-2013
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-013-1196-1

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