Combined modality therapy for primary CNS lymphoma.

DeAngelis, Lisa M.; Yahalom, Joachim; Thaler, Howard T.; Kher, Uma

doi:10.1200/jco.1992.10.4.635

Cited by 502 publications

(227 citation statements)

References 34 publications

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“…However, the significant association between a DI MTX 41000 mg m À2 week À1 and higher AUC MTX levels seems to suggest that, when administered every 3 -4 weeks, a MTX dose X3000 mg m À2 could produce better results than lower doses. This also seems to be supported by the MSKCC and RTOG experience (Deangelis et al, 1992(Deangelis et al, , 2002. In a previous trial (Deangelis et al, 1992), MTX administered at a dose of 1 g m À2 produced an overall response rate of 64% and a 5-year OS of 28%, while, in a recently reported trial (Deangelis et al, 2002), the use of a 3.5-g m À2 MTX dose produced an overall response rate of 90% and a 5-year OS of 50%.…”

Section: Discussionmentioning

confidence: 64%

“…This also seems to be supported by the MSKCC and RTOG experience (Deangelis et al, 1992(Deangelis et al, , 2002. In a previous trial (Deangelis et al, 1992), MTX administered at a dose of 1 g m À2 produced an overall response rate of 64% and a 5-year OS of 28%, while, in a recently reported trial (Deangelis et al, 2002), the use of a 3.5-g m À2 MTX dose produced an overall response rate of 90% and a 5-year OS of 50%. Analysed together, these data suggest that a higher amount of MTX administered in a single dose increases drug exposure and activity.…”

Section: Discussionmentioning

confidence: 64%

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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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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 64%

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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“…Intraocular lymphoma has a poor prognosis with a median survival of just over 3 years with treatment, 2 and once CNS involvement occurs, an untreated median survival is 1.8-3.3 months. 3 Aggressive modern-day treatments can prolong this median survival to 40 months, 4 with ocular management improving vision during this time. Primary ocular NHL often presents as a masquerade syndrome with features of posterior uveitis, which can result in diagnostic delays.…”

Section: Introductionmentioning

confidence: 99%

Cytopathological analysis of vitreous in intraocular lymphoma

Intzedy

Teoh

Hogan

et al. 2007

Eye

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Objective To describe the cytopathological method used in the analysis of vitreous samples in the diagnosis of primary intraocular lymphoma (PIOL). Participants Seven patients with refractory posterior uveitis referred to a regional ocular inflammatory service were diagnosed as having PIOL between 1999 and 2006. Methods Clinical features of the uveitis and cytopathological preparation of the samples were described. All patients underwent vitrectomy and samples were placed in formal saline or prepared fresh. Following paraffin embedding generating a cell block, immunostaining, and polymerase chain reactions were performed. Results Five women (71.4%) and two men (28.6%) (mean age 67.7 years) were included. Five patients had diagnostic vitrectomy performed within 6 months of presentation, but in two patients diagnosis was delayed up to 2 years. Uveitis was bilateral in two patients. Cytologic and immunohistochemical staining prepared from the vitreous specimens showed PIOL in all patients, and PCR displayed single band of immunoglobulin heavy chain rearrangement in five out of six samples tested. Conclusions Diagnosis of PIOL is difficult due to small volume of sample with low number of malignant cells and inadequate preparation of samples. Our method of analysis with fresh samples together with immunohistochemistry and PCR analysis demonstrates a high yield of diagnosis reducing diagnostic delay.

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“…PIOL is aggressive, and most patients with the disease die within 5 years of diagnosis. 97 Recent data suggest that prompt therapy can improve prognosis. 76 Since initiation of therapy requires an accurate diagnosis, it is essential to identify lymphoma cells in the eye.…”

Section: Discussionmentioning

confidence: 99%