Phase II Study of the Efficacy and Safety of High-dose Pemetrexed in Combination with Cisplatin Versus Temozolomide for the Treatment of Non-small Cell Lung Cancer with Brain Metastases.

The aim of this study was to explore the efficacy and safety of high-dose pemetrexed with cisplatin versus combination with temozolomide in patients with brain metastases (BM) of lung adenocarcinoma. After standard whole-brain radiotherapy (WBRT, 30 Gy/10 fractions), patients with BM of non-small cell lung cancer (NSCLC) were given high-dose pemetrexed (900 mg/m2 ) on day 1 of each cycle (3 weeks), and cisplatin was administered on days 1-3 in the cisplatin-treated group. The temozolomide-treated group was treated as follows: 75 mg/m2 temozolomide orally with concurrent WBRT followed by 150 mg/m2 temozolomide on days 1-5 with high-dose pemetrexed (900 mg/m2 ) on day 1 of each cycle (3 weeks). Six cycles later, high-dose pemetrexed (900 mg/m2 ) monotherapy or the best available supportive therapy was administered to both groups. An evaluation was carried out every 2-3 cycles. The primary end-points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Secondary end-points included safety and tolerability. Thirty-two patients in the pemetrexed plus cisplatin (PC) group and 28 patients in the pemetrexed plus temozolomide (PT) group were enrolled from November 2013 to October 2015. The ORR was 68.8% and 75%, in the PC and PT groups, respectively, and there was no statistically significant difference between the two groups (p=0.711). The median PFS rates of the PC and PT groups were 13.6 months and 16.9 months, respectively, and the median OS rates of the PC and PT groups were 18.9 months and 19.3 months, respectively. There were no differences in PFS and OS between the two groups. There were no grade 4 or higher side-effects in either group, but grade 3 side-effects such as leucopenia (2/32, 6.3%), nausea/vomiting (2/32, 6.3%), alopecia (1/32, 3.1%), rash (3/32, 9.4%) and renal insufficiency (1/32, 3.1%) were observed in the PC group, whereas the PT-group-only showed the following grade 3 side-effects: leucopenia (1/28, 3.6%) and nausea/vomiting (2/28, 7.1%). The data showed that the PT group achieved the same efficacy in PFS and OS as the PC group but with fewer toxicities. Therefore, high-dose pemetrexed plus temozolomide may be a better regimen for treating NSCLC with BM due to its better safety.