Platine and cytarabine-based salvage treatment for primary central nervous system lymphoma

Abstract

The aim of this study was to evaluate the efficacy and toxicity of two chemotherapy regimens based on platinum and cytarabine in association with etoposide and methylprednisolone (ESHAP) or with dexamethasone (DHAP) with or without Rituximab (± R) in patients with refractory or a relapsed Primary Central Nervous System Lymphoma (PCNSL). All consecutive patients from two French centers with refractory or relapsed PCNSL treated with ESHAP/DHAP ± R were included. We analyzed the overall response rate (ORR), toxicity and overall survival (OS) after salvage chemotherapy. Intensive chemotherapy and hematopoietic stem cell rescue (IC + HCR) was offered to patients less than 65 years of age and consisted of high-dose thiotepa, busulfan and cyclophosphamide. These results were compared with two previously reported series of PCNSL patients treated with the CYVE (high-dose cytarabine and etoposide) regimen at relapse. Twenty-two patients received a total of 60 DHAP/ESHAP cycles (median 3; range 1-5). The median age was 59 years. The ORR after salvage chemotherapy was 59%. Toxicity was mainly hematological, 18% of patients showing febrile neutropenia. There was no treatment-related death. ESHAP or DHAP regimens led to similar ORRs compared to the CYVE regimen in relapsed or refractory PCNSL, although they seemed less toxic. The therapeutic results of the ESHAP/DHAP regimens in relapsed or refractory PCNSL were also similar to those for relapsed systemic non-Hodgkin's lymphomas (sNHL). Both chemotherapies, CYVE regimen and ESHAP/DHAP are treatment options to be considered in relapsed or refractory PCNSL, especially when IC + HCR is planned as a consolidation treatment. More efforts are still needed to improve the ORR at relapse.

ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

“…The rest received dexamethasone, high dose aracytine, and cisplatin +/−R, to an overall complete remission rate of 27%. 13 In our patients, the use of ESHAP chemotherapy resulted in rapid regression of symptoms and disappearance of lesions observed in CT or MRI scans. The treatment was well tolerated; the two younger patients were stem cell mobilized, and then autologous stem cell transplantation was performed in optimal conditions.…”

Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

“…Hence, HD-MTX rechallenge may be effective in patients who have retained chemosensitivity to MTX despite previous exposure to the drug. Based on retrospective studies, other salvage therapies using conventional agents include a combination of procarbazine, lomustine and vincristine [ 89 ], temozolomide alone or with rituximab [ 90 , 91 , 92 ], pemetrexed [ 93 , 94 , 95 , 96 ], topotecan [ 97 , 98 ], platinum-based polychemotherapy [ 99 ], a combination of etoposide, ifosfamide and cytarabine [ 100 ], and a combination of ifosfamide, carboplatin and etoposide [ 101 ]. None of these studies was specifically devoted to elderly patients, but each included patients older than 60 years.…”

<p>Systemic Approach to Recurrent Primary CNS Lymphoma: Perspective on Current and Emerging Treatment Strategies</p>

“…High-dose cytarabine (Ara-C) has been used as single agent and in combination with other agents. [39][40][41][42] In a retrospective analysis on long-term survival of patients with PCNSL, 15 of 31 patients had relapsed after initial CR. Three patients were treated with cytarabine alone, yielding a CR in 2 and a PR in 3 patients.…”

“…As the two latter regimens were combination therapies, it is not possible to assess the impact of cytarabine versus the other regimens studied. 42 Ifosfamide Ifosfamide-based regimens have been studied in r/r PCNSL.…”