Salvage Treatment with Intracerebrospinal Fluid Thiotepa in Patients with Leptomeningeal Metastasis After Failure of Methotrexate-based Treatment

Anticancer Res. 2015 Oct;35(10):5631-8.

Abstract

Aim: To evaluate the efficacy of intracerebrospinal fluid (intra-CSF) thiotepa in patients with leptomeningeal metastasis (LM) after failure of a methotrexate-based treatment.

Patients and methods: We retrospectively reviewed the medical records of patients with LM who received 10 mg of intra-CSF thiotepa twice a week.

Results: Out of 40 patients, 25 were females (63%), and 31 (78%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Fourteen out of the 30 evaluable patients (47%) had a cytological response to intra-CSF thiotepa. The median overall survival (OS) after treatment with thiotepa was 19.4 weeks (95% confidence interval (CI)=15.3-23.5). Grade 3 toxicities were thrombocytopenia (N=2), bacterial meningitis (N=2), and pneumonia (N=1). According to a multivariate analysis, an ECOG PS ≥2 (hazard ratio (HR)=5.11, 95% CI=1.39-18.80, p=0.014), clinical improvement (HR=0.09, 95% CI=0.03-0.29, p<0.001), and radiation for LM after intra-CSF thiotepa (HR=0.33, 95% CI=0.11-0.97, p=0.043) were independently associated with survival.

Conclusion: Intra-CSF thiotepa seems to be a meaningful salvage treatment for patients with LM whose disease progresses after a methotrexate-based treatment.

Keywords: Leptomeningeal metastasis; intracerebrospinal fluid chemotherapy; methotrexate; thiotepa.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Spinal
  • Male
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / mortality
  • Meningeal Neoplasms / secondary
  • Methotrexate / pharmacology*
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Prognosis
  • Retrospective Studies
  • Salvage Therapy*
  • Survival Rate
  • Thiotepa / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Thiotepa
  • Methotrexate