Abstract

ABSTRACT Background Folate antimetabolite pemetrexed was approved for treatment of patients with metastatic non small-cell lung carcinoma (NSCLC). Its activity on brain metastases makes it attractive in combination with whole brain radiation therapy (WBRT), but this regimen could also potentially increase toxicity. Patients and treatment We retrospectively assessed the use of pemetrexed concurrently with WBRT in 12 consecutive patients with brain metastases from NSCLC. Patients received pemetrexed 500 mg/m2, either alone (n = 4) or combined with cisplatin 75mg/m2 (n = 6) or carboplatin AUC5 (n = 2). Median total number of pemetrexed-based chemotherapy cycles was 3.5 (range: 1–8). In the course of chemotherapy, patients received WBRT delivering 30 Gy in 10 fractions (n = 8) or 20 Gy in 5 fractions (n = 4). Results Six patients improved neurologically with treatment (five complete and one partial responses). Four patients had their neurological symptoms stable. Best radiological response was complete response lasting until last follow-up in one patient. Five patients experienced partial response. One patient had stable disease. Progressions were identified in four patients, within a median time interval of 17 weeks (range: 6–58 weeks). Three patients were not analyzable for tumor response because of rapid systemic progression leading to death. Two of them had improved neurologically. No high-grade WBRT-toxicity was reported but one patient developed symptoms suggestive of a limbic encephalopathy five weeks after WBRT completion. Conclusion The combination of pemetrexed with WBRT was associated with a substantial improvement of neurological deficits and tumor responses in most patients. However, survival remained disappointing and there were concerns about toxicity in one patient. A clinical trial is required for better analyzing the potential synergistic effects of drug with radiation and evaluating neurological toxicity. Disclosure All authors have declared no conflicts of interest.

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