High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study

Ann Oncol. 2009 Feb;20(2):319-25. doi: 10.1093/annonc/mdn628. Epub 2008 Oct 26.

Abstract

Background: To improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved for patients not responding to chemotherapy.

Patients and methods: High-dose MTX was applied on days 1, 15, and 30, procarbazine on days 1-10, and CCNU on day 1. Study treatment comprised up to three 45-day cycles. There was no lower limit of Karnofsky performance status (KPS).

Results: Thirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57-79 years). The median initial KPS was 60% (range 30%-90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34-105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy.

Conclusion: The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Anemia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / radiotherapy
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Leukopenia / chemically induced
  • Lomustine / administration & dosage*
  • Lomustine / therapeutic use
  • Longitudinal Studies
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pilot Projects
  • Procarbazine / administration & dosage*
  • Procarbazine / adverse effects
  • Procarbazine / therapeutic use
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Survival Analysis
  • Thrombocytopenia / chemically induced
  • Time Factors
  • Treatment Outcome

Substances

  • Procarbazine
  • Lomustine
  • Methotrexate