Journal of Neuro-Oncology

, Volume 112, Issue 2, pp 247–255 | Cite as

Pharmacokinetics and efficacy of pemetrexed in patients with brain or leptomeningeal metastases

  • Priya Kumthekar
  • Sean A. Grimm
  • Michael J. Avram
  • Virginia Kaklamani
  • Irene Helenowski
  • Alfred Rademaker
  • Mary Cianfrocca
  • William Gradishar
  • Jyoti Patel
  • Mary Mulcahy
  • Katie McCarthy
  • Jeffrey J. Raizer
Clinical Study

Brain metastases (BM) and leptomeningeal metastases (LM) are devastating neurologic complications. Pemetrexed is a multi-targeted anti-folate agent approved for treatment of nonsquamous non-small cell lung cancer but has anti-tumor activity in other solid tumors. We performed two trials using pemetrexed in patients with BM and LM to assess CSF penetration and anti-tumor activity. Patients were treated with intravenous pemetrexed at doses of 500 (n = 3), 750 (n = 3), 900 (n = 12) or 1,050 mg/m2 (n = 3) every 3 weeks. Neuro-imaging was done every 6 weeks. Matched CSF and plasma samples were obtained serially from three patients with Ommaya reservoirs; the remaining patients had a single paired collection. Twenty-one patients (15 women and six men) with median age of 50 years and median KPS of 90 were treated. Primary tumors included breast (13), lung (4), colorectal (1), endometrial (1), esophageal (1) and pinealoblastoma (1). Nine patients had prior whole brain RT and median number of prior chemotherapies was two including prior methotrexate in four patients. Median pemetrexed doses administered was three (range 1–14). Responses included one partial response, ten stable disease and ten progressive disease. Median time to progression and survival was 2.7 and 7.3 months; PFS six was 22 %. No major toxicities were seen. Pemetrexed distributed from the plasma to the CSF within 1–4 h with the resulting CSF concentrations < 5 % of plasma. Pemetrexed was tolerated in solid tumor patients with CNS metastases. Limited anti-tumor activity was seen, which might have been due to low CSF concentrations, although some patients displayed prolonged benefit.


Brain metastases Leptomeningeal metastases Pemetrexed Pharmacokinetics 



Study was supported by Lilly Oncology (research support for JJR).

Conflict of interest

None for Priya Kumthekar, Sean A. Grimm, Michael J. Avram, Virginia Kaklamani, Irene Helenowski, Alfred Rademaker, Mary Cianfrocca, William Gradishar, Jyoti Patel, Mary Mulcahy, Katie McCarthy; Jeffrey J. Raizer has research funding from Lilly Oncology.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Priya Kumthekar
    • 1
  • Sean A. Grimm
    • 5
  • Michael J. Avram
    • 2
  • Virginia Kaklamani
    • 3
  • Irene Helenowski
    • 4
  • Alfred Rademaker
    • 4
  • Mary Cianfrocca
    • 6
  • William Gradishar
    • 3
  • Jyoti Patel
    • 3
  • Mary Mulcahy
    • 3
  • Katie McCarthy
    • 1
  • Jeffrey J. Raizer
    • 1
    • 7
  1. 1.Departments of NeurologyNorthwestern UniversityChicagoUSA
  2. 2.Departments of AnesthesiologyNorthwestern UniversityChicagoUSA
  3. 3.Internal Medicine-Hematology/Oncology DivisionNorthwestern UniversityChicagoUSA
  4. 4.Division of Preventive MedicineNorthwestern UniversityChicagoUSA
  5. 5.Department of NeurologyUniversity of MinnesotaMinneapolisUSA
  6. 6.Banner MD Anderson Cancer CenterGilbertUSA
  7. 7.Feinberg School of Medicine, Northwestern UniversityChicagoUSA

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