Erlotinib with pemetrexed and cisplatin for lung cancer that has spread to the brain

The objective of this study was to evaluate the effect of erlotinib (Tarceva) in combination with pemetrexed (Alimta) and cisplatin (Platinol) in lung cancer that had spread into the brain (brain metastases).

Lung adenocarcinoma is the cancer of glandular cells of lungs. It is a common type of non-small cell lung cancer (NSCLC). In 30-40% of lung adenocarcinoma, the cancer spreads into the brain. 

In a previous study, erlotinib in combination with pemetrexed showed effectiveness in advanced lung adenocarcinoma.  It is speculated that erlotinib in combination with pemetrexed and cisplatin could be more effective in treating advanced lung adenocarcinoma. 

In this analysis, 6 lung adenocarcinoma patients with brain metastases were enrolled. In 5 of the 6 patients, EGFR genes (proteins involved in signaling within cells) were mutated (permanently changed) in tumor cells. All of them had earlier showed initial good response to gefitinib (Iressa), a drug that stops EGFR signalling in tumor cells, but were later  resistant to it.  All patients in this study received combination therapy of erlotinib with pemetrexed and cisplatin for at least 4 cycles, each cycle consisting of 21 days.

Overall, 1 patient showed complete disappearance of signs and symptoms of cancer, two patients showed partial disappearance of signs and symptoms and 2 had stable disease condition (no change in disease status). The average time until progression of brain metastases was 7 – 8.5 months. To date, 4 of the patients have died. The average survival time after the treatment was 9 months

All patients showed improvement in general well being. The combination therapy was well tolerated with few moderate side effects including mild/moderate rash and diarrhea. 

In conclusion, erlotinib in combination with permetrexed and cisplatin could be a safe and effective treatment in patients with advanced, EGFR mutated lung adenocarcinoma who have progressed despite previous gefitinib treatment. 

This study is limited by very few numbers of patients.  Clinical trials in large group of patients are needed to confirm the effectiveness of this combination therapy in lung adenocarcinoma with brain metastases.