Phase II Study of High-Dose Pemetrexed Plus Cisplatin as First-Line Chemotherapy In the Treatment of Patients with Brain Metastases from Lung Adenocarcinoma.

Background: Brain metastases (BMs) occur in up to 40% of patients with nonsmall-cell lung cancer (NSCLC). When surgery or radiosurgery is not possible, whole-brain radiotherapy (WBRT) is the standard treatment, with a cerebral response rate of approximately 30%. Pemetrexed-based chemotherapy presents an approximately 40% response rate on brain lesions of NSCLC with brain metastases.

Methods: This trial assessed the efficacy and safety of high-dose pemetrexed plus cisplatin in NSCLC with BMs after WBRT. Thirty-two patients with Karnofsky Performance Status ≥70 were enrolled. Patients of NSCLC with brain metastases were eligible for WBRT, which was administered at 30 Gy/10f. Thereafter, high-dose pemetrexed plus cisplatin was given up to 6 cycles. Primary end point was objective response rate (RR) and progression-free survival on BM. Secondary end points included extracerebral and overall RR, safety profile, and survival.

Results: The objective cerebral RR (complete and partial response) was 68.8 % (22 of 32 patients). Extracerebral and globe RR was 37.5% and 31.3%, respectively. The median progression-free survival of BM was 13.6 months, and median overall survival was 19.1 months.

Conclusions: This modality of treatment appears to a better efficacy and a good safety of BM, as well as extracerebral. Further clinical studies are warranted.