High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma

Cancer Sci. 2016 Oct;107(10):1458-1464. doi: 10.1111/cas.13012. Epub 2016 Sep 1.

Abstract

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

Keywords: Central nervous system disease; interleukin-10; intraocular lymphoma; methotrexate; uveitis.

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Biomarkers
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / prevention & control*
  • Central Nervous System Neoplasms / secondary*
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunophenotyping
  • Intraocular Lymphoma / drug therapy*
  • Intraocular Lymphoma / metabolism
  • Intraocular Lymphoma / mortality
  • Intraocular Lymphoma / pathology*
  • Intravitreal Injections
  • Kaplan-Meier Estimate
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers
  • Cytokines
  • Methotrexate