What Is The Optimal Dose Of Methotrexate In Primary Central Nervous System Lymphoma Treatment Regimens?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3040-3040
Author(s):  
Samir Dalia ◽  
Samantha L Price ◽  
Peter Forsyth ◽  
Celeste M. Bello ◽  
Bijal D. Shah ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Total Dose ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Significant Difference ◽  
Treatment Data ◽  
Dose Reductions

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a rare disorder with a poor prognosis. The mainstay of treatment is single agent or combination high dose (≥3.5g/m2) methotrexate (HDMTX) based regimens. There is no consensus as to which dose of HDMTX improves outcomes in patients with PCNSL but doses of MTX greater than 3 g/m2 intravenously achieve therapeutic cerebrospinal fluid (CSF) concentrations. Purpose To determine if there is an optimal or total dose of HDMTX in PCNSL therapies that results in improved progression free (PFS) or overall survival (OS). Methods Patients at Moffitt Cancer Center with PCNSL were identified using our institutional database between January 1, 2000 and September 30, 2011. Patients with complete treatment data who were treated with HDMTX were included in this study. HDMTX was defined as MTX at a dose ≥ 3.5g/m2. Patient demographics, clinical, and treatment data were collected and analyzed. Treatment information collected included the starting dose of HDMTX, IV rituximab use, MTX toxicity and clearance, cycles of MTX, and total amount of MTX administered (g/m2). Data were analyzed using descriptive statistics and the Kaplan-Meier (KM) method was used to estimate median PFS and OS using the log rank test. P value of <0.05 was considered significant. All data was analyzed using SPSS statistical software version 21.0. Results A total of 51 patients were identified (Table 1). Median PFS was 13months (0-33) and median OS 43months (29-57). The addition of IV rituximab or other chemotherapy failed to improve PFS or OS. HDMTX dose reductions or the total dose of HDMTX administered did not significantly impact PFS or OS. Similarly, when comparing dosing of HDMTX there was no significant difference in 8g/m2 versus 3.5g/m2 (PFS p=0.56, OS p=0.68), or between patients receiving 8g/m2 versus <8g/m2 (PFS p=0.77, OS p=0.6) (Figure 1). Patients receiving 8g/m2 versus those receiving <8g/m2 of HDMTX had similar baseline characteristics except for more liver function abnormalities in the 8g/m2 group. Conclusions Differences in initial dosing of HDMTX or total dose of HDMTX therapy did not influence outcomes in our patients with PCNSL. Dose reductions in HDMTX, addition of other chemotherapeutic agents, or rituximab were not associated with improved PFS or OS. An intriguing plateau was observed in OS in the 8gm/m2 arm despite similar PFS, suggesting that the receipt of novel therapies in the relapsed setting may contribute to OS. Multicenter collaborative clinical trials are needed to further assess the optimal initial dose of HDMTX to administer in PCNSL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficacy and Toxicity of Treatments for Primary Central System Lymphoma: Review of the Recent Literature

2019 ◽  
Vol 9 (1) ◽  
pp. 61-67
Author(s):  
Mohammad Jay ◽  
David. A. MacDonald
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Benefit ◽  
Radiation Treatment ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Wide Range

Primary Central Nervous system lymphoma (PCNSL) is an uncommon type of central nervous system lymphoma, most commonly presenting as hemiparesis and headache. Currently, there is a wide range of treatments for PCNSL, consisting of various permutations between chemotherapy, radiation and autologous stem cell transplant (ASCT). Although the backbone of PCNSL treatment consists of High-dose Methotrexate (HD-MTX), the role of combination versus single agent chemotherapy, combined modality (chemotherapy + radiation) versus chemotherapy or radiation alone, and the use of consolidative ASCT are contested. Surgery does not have a role in the treatment of PCNSL although stereotactic biopsies tend to help with symptomatic relief. Radiation monotherapy is generally reserved for patients with contraindications to chemotherapy or as a palliative measure. Combined chemotherapy and radiation treatment has been shown to have a great efficacy, although its increased neurotoxicity compared to chemotherapy alone is a major drawback. A growing body of research is focused on comparing the efficacy of various chemotherapeutic regimens. Currently, the MATRix regimen comprising of HD-MTX(3.5g/m2)-cytarabine/rituximab/thiotepa is widely used. The additional survival benefit of ASCT is contested although its role in the treatment of refractory or relapsed PCNSL is generally agreed upon. Finally, intrathecal HD-MTX has been shown to have added survival benefit when added to the standard therapies. Further retrospective and prospective studies are required to compare the efficacy and toxicity of various treatment options, with a focus on different chemotherapeutic agents and ASCT.

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

scholarly journals LINC-33. MULTIMODALITY MANAGEMENT OF PAEDIATRIC PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA- UPDATED EXPERIENCE FROM A REGIONAL CANCER CENTRE IN NORTH INDIA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii385-iii385
Author(s):  
Ahitagni Biswas ◽  
Swarnaditya Roy ◽  
Yousra KN ◽  
Sameer Bakhshi ◽  
Vaishali Suri ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
North India ◽  
High Dose ◽  
Ocular Involvement ◽  
Csf Cytology ◽  
Whole Brain ◽  
Female Ratio

Abstract Paediatric primary central nervous system lymphoma(PCNSL) constitutes 1% of all PCNSLs. Data pertaining to paediatric PCNSL (2016–19) was abstracted by retrospective chart review. We identified 7 paediatric patients with PCNSL. None had congenital or acquired immunodeficiency. The median age at presentation was 13 years. The male to female ratio was 4:3. The median ECOG performance status was 2. On neuro-imaging, 3 patients had solitary and 4 patients had multiple lesions. CSF cytology showed atypical cells in 1 patient. None had ocular involvement. Systemic lymphoma work-up was negative in all. Biopsy and resection of tumour were done in 4 patients each. Histopathology revealed DLBCL in 6 and B-cell NHL in 1 patient. All patients underwent induction chemotherapy (median-5 cycles)- modified DeAngelis protocol (IV Methotrexate-2.5g/m2,IT Methotrexate-12 mg,Vincristine,Procarbazine and Rituximab-375mg/m2 every 2 weeks) in 6 and single agent Methotrexate -3.5g/m2 every 3 weeks in 1 patient. Severe haematological toxicities included grade 3 neutropenia, leucopenia and febrile neutropenia in 2,1 and 1 patient respectively. Radiotherapy(RT) was administered in all-whole brain RT(36-45Gy/20-25fractions/4-5weeks) in 6 patients and craniospinal RT(36Gy/18fractions/3.5weeks) followed by whole brain RT(9Gy/5fractions/1week) in 1 patient(with positive CSF cytology). Subsequently consolidation chemotherapy with 2 cycles of Cytarabine(3g/m2 IV D1-2 every 3 weeks) was administered in 5 patients. After a median follow-up of 14 months(mean-18.2 months), all patients are in complete radiological remission. Paediatric PCNSL is a rare tumour entity and multimodality management with high dose Methotrexate and Rituximab based chemo-immunotherapy and cranial radiotherapy leads to excellent early clinical outcome.

Chemotherapy for primary central nervous system lymphoma

2006 ◽  
Vol 21 (5) ◽  
pp. 1-8 ◽  
Author(s):  
Antonio M. P. Omuro ◽  
Lauren E. Abrey
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Randomized Trials ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
High Dose ◽  
Dose Methotrexate ◽  
Intensified Chemotherapy ◽  
Relapse Rates

✓Chemotherapy, with or without radiotherapy, is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, and it is used in doses of 1 to 8 g/m2, either as a single agent or in combination with other drugs such as corticosteroid agents, cytarabine, procarbazine, vincristine, carmustine, lomustine, thiotepa, cyclophosphamide, temozolomide, and rituximab. To date, an overwhelming number of different regimens in which high-dose MTX is used have been reported. Given the lack of randomized trials, however, the optimal treatment remains controversial. Varying methodology makes the comparison of available studies extremely difficult, yet some common themes can be found throughout the literature. Treatment paradigms vary considerably according to the patient's age. Most studies support the use of chemotherapy-only treatments for elderly patients (> 60 years), given the high risks of neurotoxicity associated with radiotherapy. Nevertheless, the prognosis remains poor regardless of the chemotherapy chosen, and less toxic regimens might be preferable for such elderly patients. Conversely, in younger patients (< 60 years), there is growing evidence that commonly used chemotherapy-only regimens are associated with increased relapse rates that may not justify deferral of radiotherapy. Thus, a significant focus of research has been the development of intensified chemotherapy regimens that could replace radiotherapy. In this article, the authors discuss the principles guiding the use of chemotherapy for PCNSL, and critically review the available literature, including the most recent trials.

A retrospective analysis of cost and survival outcomes based on consolidation regimens in primary central nervous system lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14544-e14544
Author(s):  
Savannah Gelhard ◽  
Amiee Maxwell ◽  
Howard Colman ◽  
Adam Louis Cohen ◽  
Joe Sammy Mendez
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Cost Benefit ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Consolidation Therapy ◽  
Treatment Regimens ◽  
Comparative Cost ◽  
The Cost

e14544 Background: Treatment for Primary Central Nervous System Lymphoma (PCNSL) includes induction therapy consisting of polychemotherapy including high-dose methotrexate followed by consolidation therapy. There are various induction and consolidation regimens with wide variability in their treatment duration, inpatient vs outpatient administration, and the number of chemotherapeutic agents utilized. We performed a comparative cost and efficacy analysis of three consolidation techniques in an effort to provide insight into the cost-benefit of these treatment regimens. Methods: Patients treated for newly diagnosed PCNSL at our institution after July 1, 2012 were retrospectively reviewed. Patients who completed one of the following regimens and received consolidation therapy at our institution were included: rituximab/methotrexate/vincristine/procarbazine (R-MVP), rituximab/methotrexate/temozolomide (R-MT), or rituximab/methotrexate (R-M) for induction followed by consolidation with etoposide/cytarabine (EA), high-dose cytarabine (HIDAC), or high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR). Cost to health system was derived from a Value Driven Outcomes tool and filtered to compare major costs of treatment. Survival was calculated from the date of diagnosis and last date of known survival. Results: Twenty-two patients met eligibility criteria and received the following four treatment regimens: R-MT+EA (12), R-MT+ HDC-ASCR (3), R-M+ HDC-ASCR (1), and R-MVP+HIDAC (6). Patients receiving HDC-ASCR (4) had a trend towards a more favorable overall survival (p = 0.0880) compared to the other two consolidation therapies with no recurrence or death in those patients treated with HDC-ASCR. Comparative cost analysis of facility and pharmacy costs of the three consolidation techniques found that HDC-ASCR was 40 times the cost of the cheapest treatment, HIDAC. Conclusions: This small retrospective review provides evidence that HDC-ASCR may be a superior consolidation strategy but with a profound increase in financial cost. To our knowledge this is the first study completed in the U.S. comparing treatment outcomes and cost in PCNSL. Based on our results, it is clear that a larger and prospective review could potentially shed light on selecting a standard of care based on cost-benefit analysis.

Significance of MYC rearrangement and chemotherapy type on survival outcomes of patients with central nervous system lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7548-7548
Author(s):  
Natalie Sophia Grover ◽  
Allison Mary Deal ◽  
Stephanie Mathews ◽  
Ashley Freeman ◽  
Christopher Dittus ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Statistical Significance ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
High Dose ◽  
Single Institution ◽  
Significant Difference

7548 Background: Central nervous system lymphoma (CNSL) has a poor prognosis and an optimal treatment regimen has not been established. Due to the rarity of this disease and frequently poor performance status at diagnosis, there have been few prospective therapeutic clinical trials in this patient population. We therefore performed a retrospective analysis of prognostic factors and treatment outcomes of patients with CNSL treated at a single institution. Methods: Pathology records were used to identify patients diagnosed with CNSL from 1/1/2005 to 9/1/2016 at the University of North Carolina Cancer Hospital. Information about demographics, disease characteristics, treatment, and outcomes was gathered from the electronic medical record. Overall (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Results: We identified 100 patients with CNSL. 49% had primary CNSL (PCNSL). 78% of cases were diffuse large B cell lymphoma. Out of 51 patients evaluated for MYC translocation by FISH, 13 were positive (3 PCNSL and 10 secondary CNSL). Out of 74 patients treated with chemotherapy, 51% received methotrexate (MTX), procarbazine, and vincristine (MPV), with or without rituximab, 28% were treated with other high dose MTX based regimens, with or without rituximab, and 20% received a non-MTX based regimen. There was no significant difference in OS between PCNSL and secondary CNSL (13.7 vs 7.9 months, p = 0.97). Patients with MYC translocation had a worse OS compared to those without MYC translocation (5.1 vs 29.5 months, p = 0.004). Patients treated with MPV had a longer PFS compared to those treated with other high dose MTX based regimens or those who were treated with a non-MTX based regimen (19.1 vs 10.9 vs 3.9 months, p = 0.05), but difference in OS did not reach statistical significance (29.5 vs 22.4 vs 10.6 months, p = 0.12). Conclusions: In this single institution analysis of CNSL, MYC translocation was associated with worse survival. MPV was associated with improved PFS compared to other chemotherapy regimens. Further prospective studies are needed comparing MPV to other MTX-based regimens in CNSL.

Ibrutinib-based combination therapy exhibited therapeutic benefit in newly diagnosed primary central nervous system lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2556-2556
Author(s):  
Feili Chen ◽  
Diwen Pang ◽  
Hanguo Guo ◽  
Qiuxiang Ou ◽  
Xue Wu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Combination Therapy ◽  
De Novo ◽  
Single Agent ◽  
Objective Response ◽  
Central Nervous System Lymphoma ◽  
High Dose ◽  
Induction Phase ◽  
Newly Diagnosed

2556 Background: Ibrutinib has shown single-agent activity in relapse/refractory (R/R) primary central nervous system lymphoma (PCNSL), and the high dose methotrexate (HD-MTX) has been the backbone of treatment of de-novo PCNSLs. Combination therapy of HD-MTX and ibrutinib has recently shown activity in R/R PCNSLs. Methods: Eleven newly diagnosed PCNSL patients who underwent combination therapy of HD-MTX and ibrutinib were analyzed for treatment response and safety profile. HD-MTX was given at 3.5 g/m2 every 2 weeks for a total of 8 doses. Ibrutinib was held on days of HD-MTX infusion until HD-MTX clearance. Single-agent daily ibrutinib was administered continuously after completion of induction therapy until disease progression, intolerable toxicity, or death. Patients’ clinicopathologic characteristics were retrospectively reviewed and genomic traits were further analyzed. Results: Nine out of 11 patients have completed the induction phase of ibrutinib-based combination therapy and received ibrutinib maintenance in addition to two patients whose disease progressed during the therapy. An objective response rate (ORR) of 82% (9/11) was observed, including 7 patients with complete response (CR, 64%) and 2 patients with partial response (PR, 18%). The median progression-free survival (PFS) was 7.4 months while the median overall survival (OS) was not reached. The combination therapy of HD-MTX and ibrutinib was well tolerated and has acceptable safety. In addition, the presence of ctDNA in cerebrospinal fluid (CSF) samples closely correlated with tumor response. Sustained tumor responses were associated with the clearance of ctDNA from the CSF. Conclusions: Combination of ibrutinib and HD-MTX has acceptable safety and has demonstrated anti-tumor activity in newly diagnosed de-novo PCNSL patients. The detection of ctDNA in CSF is feasible for monitoring tumor burden in PCNSL patients.

scholarly journals ML-04 The influence of surgical intervention for high-dose Methotrexate chemotherapy in the patients with primary central nervous system lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii15-ii16
Author(s):  
Michinari Okamoto ◽  
Shigeru Yamaguchi ◽  
Yukitomo Ishi ◽  
Hiroaki Motegi ◽  
Hiroyuki Kobayashi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Surgical Resection ◽  
Chronic Subdural Hematoma ◽  
Central Nervous System Lymphoma ◽  
University Hospital ◽  
Postoperative Treatment ◽  
High Dose ◽  
Significant Difference ◽  
Methotrexate Chemotherapy

Abstract Object: Surgical resection is not the standard of treatment for primary central nervous system lymphoma (PCNSL). Some recent studies suggest that resection might be beneficial. The aim of this study was to examine the effect of surgical treatment in terms of the time from surgery to chemotherapy. Methods: We retrospectively analyzed all patients with PCNSL treated at Hokkaido University Hospital between 2001 and 2018 to assess the effect of selection for resection on the response of Methotrexate chemotherapy. We identified the days from surgery to chemotherapy, complications, the response of Methotrexate (CR/CRu rate) and prognostic factors including progression free survival (PFS) and overall survival (OS). Results: A total 105 patients were identified. 84 patients underwent biopsy and 21 patients underwent surgical resection. Their median age were 63 [31–78] and 68 [44–77], respectively. Their Karnofsky Performance Status (KPS) were 70 [30–100] and 70 [40–100]. There were any significant difference. Patients undergoing biopsy and those undergoing resection had comparable rates of complications for all complication type. Overall, 4 biopsy patients and 5 resection patients experienced at least one complication. They were composed of 2 asymptomatic bleeding, 1 wound abscess, 1 hydrocephalus in biopsy patients, 1 epidural abscess, 1 epilepsy, 1 chronic subdural hematoma, 2 temporary hemiparesis. Although the days from surgery to chemotherapy were significantly shorter in patients underwent biopsy than in those underwent resection (P=0.0015), PFS was significantly longer in patients underwent resection than in those underwent biopsy (P=0.0403), whereas there was no difference in OS. Discussion: Resection could delay the postoperative treatment. In this study, there was a significant delay of postoperative treatment in resection patients, however, CR/CRu rate after MTX was significantly better in those underwent resection than biopsy. We can see that resection for PCNSL might not necessarily worsen the prognosis.

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