Intra-CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

Kurt A. Jaeckle, Jesse G. Dixon, Stephen Keith Anderson, Alvaro Moreno-Aspitia, Gerardo Colon-Otero, Kathy Hebenstreit, Tejal A. Patel, Samarth L. Reddy, Edith A. Perez

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: There are few treatment options for patients with leptomeningeal metastases (LM). Methods: We report a case series of patients with breast cancer and LM treated with intra-CSF topotecan (TOPO). Outcome was assessed by clinical exam and MRI at baseline, at end of induction (4-5 weeks), then every 3 months; CSF cytology was determined at baseline and with each treatment. Results: Thirty-one women [median age, 58 (37-81); median KPS 60 (40-100)] received treatment. At baseline, 68% had positive CSF cytology, and 90%, leptomeningeal enhancement on MRI. 84% of patients also received focal RT (not during TOPO) and 77% received concomitant systemic hormonal or chemotherapy. Median number of TOPO treatments was 14.5 (range, 3-71); median duration of treatment, 11 weeks (1-176); and median OS, 6.9 months (range, 0.9-48.8). Patients remaining progression-free during 4-6 weeks of induction (81%) had a median OS of 11.5 months (range, 1.8-48.8). Overall neurologic PFS at 6, 12, and 24 months was 39%, 26%, and 6%, respectively. Clearing of CSF malignant cells for >3 consecutive samples occurred in 10/21 (48%) patients with positive CSF cytology at baseline, remaining clear for a median duration of 15.9 months (range, 1.4-34.5). Grade 3 adverse events included headache or vomiting (3pts), T2 hyperintensity surrounding the ventricular catheter (2 pts), and meningitis (2 pts). Conclusions: Intra-CSF TOPO, with focal RT as needed for symptomatic areas of enhancement produced durable clearing of CSF malignant cells in 48% of patients positive at baseline, with promising median PFS and OS.

Original languageEnglish (US)
Pages (from-to)7935-7942
Number of pages8
JournalCancer medicine
Issue number21
StatePublished - Nov 1 2020


  • breast cancer
  • leptomeningeal metastasis
  • neoplastic meningitis
  • topotecan

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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