Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96–07

Batchelor, Tracy T.; Carson, Kathryn A.; O’Neill, Ailbhe C.; Grossman, Stuart A.; Alavi, Jane Β.; New, Pamela; Hochberg, Fred H.; Priet, Regina

doi:10.1200/jco.2003.03.036

Cited by 490 publications

(299 citation statements)

References 27 publications

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“…Irrespective of the question, if these differences are sufficient to explain the discrepancy between our observation and data in the literature, the results of the present trial suggest, that long term tumor control in PCNSL with a polychemotherapy regimen developed by our group [3] is only possible, if local treatment of the CSF compartment is included. Since in young patients with PCNSL cure is the aim, it is disappointing, that just omitting intraventricular treatment leaves this protocol no more efficient than other less demanding regimens [15][16][17]. However, a possible role of the CSF compartment as a sanctuary for lymphomatous tumor cells in PCNSL is suggested by this observation, which might be more important in chemotherapy alone protocols than previously acknowledged.…”

Section: Discussionmentioning

confidence: 93%

“…Clinical trials in PCNSL have exploited therapy with high-dose MTX alone [15][16][17], MTXbased polychemotherapy [3,18] and combination of MTX-based chemotherapy with whole brain radiotherapy [19][20][21][22][23]. MTX as a sole treatment in two multicenter trials at a dosage of 8g/m 2 every 14 days for six cycles has resulted in complete response (CR) rates of 29%/52%…”

Section: Discussionmentioning

confidence: 99%

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Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study

et al. 2008

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and 5) and cytarabine (Ara-C; cycles 3,6) based systemic therapy including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide.Results: Study accrual was prematurely stopped in 11/05 due to a high rate of early relapses.Seventeen/18 patients were assessable for response: Nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu), two (12%) partial response (PR), four (24%) showed progressive disease (PD); one treatment was stopped due to toxicity.Median follow-up is 23 months; median response duration was only ten months in responding patients and median time to treatment failure (TTF) eight months in the whole group; median overall survival (OS) has not been reached. Systemic toxicity was mainly hematologic.Conclusions: In PCNSL patients < 60 years polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with intraventricular treatment.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study

et al. 2008

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“…The choice of the MTX dose is a relevant issue in PCNSL, especially because of the high interpatient and intrapatient variability of MTX pharmacokinetics. For example, in a recently published trial (Batchelor et al, 2003), the MTX dose (8 g m À2 ) was adjusted based on the pre-chemotherapy CL crea . The dose was reduced by the percentage decrease of this variable below 100 ml min À1 .…”

Section: Discussionmentioning

confidence: 99%

Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas

Guerra²,

et al. 2004

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Although high-dose methotrexate (HD-MTX) is the most effective drug against primary CNS lymphomas (PCNSL), outcomedetermining variables related to its administration schedule have not been defined. The impact on toxicity and outcome of the area under the curve (AUC MTX ), dose intensity (DI MTX ) and infusion rate (IR MTX ) of MTX and plasmatic creatinine clearance (CL crea ) was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-based combinations. Anticonvulsants were administered in 31 pts (69%). Age 460 years, anticonvulsant therapy, slow IR MTX (p800 mg m À2 h À1 ), and reduced DI MTX (p1000 mg m À2 wk À1 ) were significantly correlated with low AUC MTX values. Seven patients (16%) experienced severe toxicity, which was independently associated with slow CL crea . A total of 18 (40%) patients achieved complete remission after chemotherapy, which was independently associated with slow CL crea . In all, 22 patients were alive at a median follow-up of 31 months, with a 3-year OS of 4079%; slow CL crea and AUC MTX 41100 mmol h l À1 were independently associated with a better survival. Slow CL crea and high AUC MTX are favourable outcome-determining factors in PCNSL, while slow CL crea is significantly related to higher toxicity. AUC MTX significantly correlates with age, anticonvulsant therapy, IR MTX , and DI MTX . These findings, which seem to support the choice of an MTX dose X3 g m À2 in a 4 -6-h infusion, every 3 -4 weeks, deserve to be assessed prospectively in future trials. MTX dose adjustments in patients with fast CL crea should be investigated. (Reni et al, 1997;Ferreri et al, 2002b). Any chemotherapy regimen without HD-MTX is associated with outcomes no better than those obtained with radiotherapy (RT) alone in these malignancies (Schultz et al, 1996;O'Neill et al, 1999;Mead et al, 2000), while the survival benefit of the addition of other drugs to HD-MTX remains a matter of debate (Reni et al, 2001;Ferreri et al, 2002b). In spite of its central role in PCNSL treatment, the optimal dose, administration schedule, and dose timing of MTX have not been clearly defined. Moreover, contrary to what is observed in other malignancies in which MTX plays a crucial role, such as acute leukaemia (Evans et al, 1986) and osteosarcoma (Graf et al, 1994;Delepine et al, 1995;Bacci et al, 1998), where a significant association between MTX parameters and outcome has been reported, the impact on toxicity and outcome of MTX administration schedule has not been investigated in PCNSL.The analysis of some MTX parameters, such as the area under the curve (AUC MTX ), dose, dose intensity (DI MTX ), and infusion rate (IR MTX ), as well as the plasmatic creatinine clearance (CL crea ) could allow us to identify subgroups of patients with increased risk of severe toxicity or disappointing outcome, as well as to define the optimal MTX administration schedule against PCNSL. This paper reports the analysis of the impact on toxicity and outcome of the above-mentioned variables in a retro...

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“…Effective combination chemotherapy regimens have been developed to incorporate methotrexate and wholebrain radiotherapy (DeAngelis et al, 2002;Batchelor et al, 2003;Wang et al, 2013). Immunotherapy, which revolutionised the treatment of systemic non-Hodgkin lymphoma, also seems to offer benefits for patients with PCNSL.…”

Section: Discussionmentioning

confidence: 99%

Fotemustine, Teniposide and Dexamethasone in Treating Patients with CNS Lymphoma

Wu¹,

Wang²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.

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Treatment of Primary CNS Lymphoma With Methotrexate and Deferred Radiotherapy: A Report of NABTT 96–07

Abstract: These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens.

Cited by 490 publications

References 27 publications

Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study

Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study

Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas

Fotemustine, Teniposide and Dexamethasone in Treating Patients with CNS Lymphoma

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