German Cancer Society Neuro‐Oncology Working Group NOA‐03 multicenter trial of single‐agent high‐dose methotrexate for primary central nervous system lymphoma

Herrlinger, Ulrich; Schabet, Martin; Brugger, Wolfram; Kortmann, Rolf‐Dieter; Küker, Wilhelm; Deckert, Martina; Engel, Corinna; Schmeck-Lindenau, H. J.; Mergenthaler, H.-G.; Krauseneck, P.; Benöhr, Christian; Meisner, Christoph; Wiestler, Otmar D.; Dichgans, J.; Kanz, Lothar; Bamberg, M.; Weller, Michael

doi:10.1002/ana.10102

Cited by 164 publications

(88 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, this regimen carries a significant risk of delayed neurotoxicity (7,9), and therefore WBRT is usually delayed or avoided and reserved for cases of tumor recurrence. Several trials have investigated the efficacy of single-agent high-dose MTX (HD-MTX) and found variable CRRs ranging from 29-52% (10,11). There is now increasing evidence that MTX-based polychemotherapy is superior to HD-MTX alone, for instance, when MTX is combined with HD-cytarabine (Ara-C) or ifosfamide (12,13).…”

Section: Introductionmentioning

confidence: 99%

Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience

Crew

Graham

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Rituximab (RTX) improves the outcome in patients with systemic diffuse large B-cell lymphoma (DLBCL), but its benefit in primary central nervous system lymphoma (PCNSL) is unclear. In the present study, a single-institution retrospective analysis was performed for 12 patients with newly diagnosed PCNSL treated with combined high-dose methotrexate (HD-MTX) and RTX. MTX was administered biweekly at 8 g/m 2 /dose until a complete response (CR) was achieved or for a maximum of eight doses. RTX was provided for a total of eight weekly doses at 375 mg/m 2 /dose. Following a median of 11 cycles of MTX, the radiographic overall response rate was 91% and the CR rate was 58%. A CR was achieved after a median 6 cycles of MTX. The median progression-free survival time was 22 months and the median overall survival time has not yet been attained. These results compare favorably to single-agent HD-MTX and suggest a role for immunochemotherapy in the treatment of PCNSL.

show abstract

Section: Introductionmentioning

confidence: 99%

Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience

Crew

Graham

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…Unlike other CNS tumors, PCNSL often shows a favorable response to chemotherapy. The majority of the active regimens include the use of highdose methotrexate (HD-MTX), which has become a standard component in the treatment of PCNSL (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

ATP-binding cassette transporters in primary central nervous system lymphoma: Decreased expression of MDR1 P-glycoprotein and breast cancer resistance protein in tumor capillary endothelial cells

Sakata

Fujiwara

Ohtsuka³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. Most tumors in the central nervous system are drug resistant partly because of the presence of the bloodbrain barrier (BBB) between circulating blood and tumor tissues. Primary central nervous system lymphoma (PCNSL) is one of the exceptions, as it is highly sensitive to high-dose methotrexate (MTX)-based chemotherapy. The aim of this study was to evaluate the BBB function of tumor capillary endothelial cells in PCNSL. Expression of three major drug efflux transporters that belong to the ATP-binding cassette (ABC) superfamily, P-glycoprotein encoded by the human multidrug resistance gene (MDR1 Pgp; ABCB1), breast cancer resistance protein (BCRP; ABCG2), and multidrug resistance-associated protein 1 (MRP1; ABCC1), was evaluated. Immunohistochemistry was performed in capillary endothelial cells of 30 tumor areas from 22 PCNSL cases and compared with that of 30 gliomas. The microenvironment around tumor capillaries was assessed by examining the distribution of astrocytes and by counting the number of macrophages and T-cells, the principal cytokine producers. In PCNSL, expression of MDR1 Pgp and BCRP in tumor capillary endothelial cells was decreased in 63 and 93% of tumor areas examined, respectively, and these reduction levels differed significantly from those of gliomas (P<0.05). When the PCNSLs were further segregated by way of infiltration of tumor cells into three patterns (dense, perivascular and sparse), decreased MDR1 Pgp and BCRP in tumor capillary endothelial cells were much more prominent in dense and perivascular patterns. In all tumors and non-tumor areas of the brain, MRP1 was undetected on capillary endothelial cells. Assessment of the microenvironment around the tumor capillaries suggested that dissociation from astrocytes and infiltration of macrophages and T-cells was involved in the down-regulation of MDR1 Pgp and BCRP in capillary endothelial cells. In conclusion, we report that expression of the major ABC transporters of the BBB, MDR1 Pgp and BCRP, decreases in tumor capillary endothelial cells of PCNSL. Thus, decreased expression may permit delivery of chemotherapeutic agents to the tumor tissues.

show abstract

“…3,9 Because of the high-risk of delayed neurotoxicity, multiple phase 2 trials have examined the efficacy of chemotherapy alone; these studies reported CR rates of 30% to 79% and median overall survivals of 14 to 50 months. [10][11][12][13][14][15] However, each study differed with regard to baseline patient characteristics, the number of chemotherapy cycles, and types of chemotherapeutic agents combined with high-dose MTX. Moreover, the overall and failure-free survival analyses included all patients on an intent-to-treat basis, and WBRT was often used for patients who had partial responses and progressive or recurrent PCNSL, strongly influencing survival data.…”

mentioning

confidence: 99%

Primary central nervous system lymphoma: The role of consolidation treatment after a complete response to high‐dose methotrexate‐based chemotherapy

Ekenel

Iwamoto

Ben-Porat

et al. 2008

Cancer

View full text Add to dashboard Cite

BACKGROUND.The most effective treatment for a new diagnosis of primary central nervous system lymphoma is high‐dose methotrexate (MTX)‐based chemotherapy followed by whole‐brain radiation therapy (WBRT). However, this combined modality treatment carries an increased risk of delayed neurotoxicity. For patients who achieve a complete response (CR) after induction that uses high‐dose MTX‐based chemotherapy, it is not clear if consolidation treatment is necessary. Therefore, a retrospective study was conducted to assess the impact of consolidation treatment after a CR to initial induction chemotherapy on disease control and survival.METHODS.The authors retrospectively analyzed 122 patients who achieved a CR after initial MTX‐based chemotherapy. The benefit of consolidation WBRT, high‐dose cytarabine (HDAC), or both on failure‐free (FFS) and overall survival (OS) was assessed.RESULTS.With a median follow‐up of 60 months, FFS was longer in patients who received WBRT plus HDAC as consolidation treatment (P = .03 by univariate analysis); there was no difference in OS observed among patients who received no consolidation treatment, HDAC alone, WBRT plus HDAC, or WBRT alone. Age and Karnofsky performance scale (KPS) were the only independent prognostic factors. Patients who received WBRT alone or in combination with HDAC had higher rates of neurotoxicity.CONCLUSIONS.Consolidation treatment with WBRT, HDAC, or both does not appear to improve survival in patients who achieved a CR with induction MTX‐based therapy. Age, KPS, and risk of delayed neurotoxicity must be considered in the choice of consolidation regimens. Cancer 2008. © 2008 American Cancer Society.

show abstract

German Cancer Society Neuro‐Oncology Working Group NOA‐03 multicenter trial of single‐agent high‐dose methotrexate for primary central nervous system lymphoma

Cited by 164 publications

References 21 publications

Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience

Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience

ATP-binding cassette transporters in primary central nervous system lymphoma: Decreased expression of MDR1 P-glycoprotein and breast cancer resistance protein in tumor capillary endothelial cells

Primary central nervous system lymphoma: The role of consolidation treatment after a complete response to high‐dose methotrexate‐based chemotherapy

Contact Info

Product

Resources

About