Abstract
Fluoropyrimidine analogues, 5FU, Capecitabine and Pemetrexate, inhibit thymidylate synthase and they have been widely used for the treatment of systemic malignancies. Capecitabine can penetrate CNS and has shown some efficacy in the treatment of breast cancers with CNS metastasis. The role of Pemetrexed in the treatment of recurrent primary and systemic malignancies with CNS metastsis is not known. We have treated 33 pts with previously heavily-treated recurrent primary and systemic malignancies with CNS metastasis based on the results of the molecular profiling. 16/33 pts were found to have TS-negative and 9/16 TS-negative patients were treated with Pemetrexed. MRI was performed every 2-3 months for tumor evaluation. Total pts: 9. M:F 5:4, Age: 48-88 yo. Median age 70.7 yo. Treatment period: 7/14 - 6/16. 1/1 GBM pt: SD for 4 mo. 1/2 anaplastic astrocytoma pts: SD for 4 mo. 1 Gr. II astrocytoma pt: SD for 7 mo. 2/2 meningioma pts: SD for 2 mo (still on treatment) and 4 mo. Both pts also received concurrent cisplatin based on ERCC1 and BRCA1 markers. 2/2 pts with squamous cell Ca of skin with skull base/brain metastasis: 1 PR for 24 mo, 1 SD for 18 mo respectively and still receiving treatment. 1 chordoma pt involving cervical/skull base: SD for 11 mo: still receiving treatment. Toxicities were very mild except 2 meningioma pts (Gr. 3-4) who also received cisplatin. Pemetrexed treatment for TS-negative recurrent primary and systemic malignancies with CNS metastasis demonstrated an excellent response rate of 89% (PR:1, SD:7, TP:1). Toxicities were minimal and tumor responses were durable. Particularly in the elderly population, in light of excellent toxicity profile, Pemetrexed should be considered as a part of the first treatment options for TS-negative CNS malignancies. A TS directed trial for pts with TS-negative recurrent CNS malignancies is warranted.
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