In a nutshell
The authors reviewed the effectiveness of a group of drugs called epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC) brain metastasis (cancer that has spread from the lungs to the brain).
Some background
There is a 20-40% risk that NSCLC will spread from the lung to the brain. There are very few effective treatments available for NSCLC brain metastases. Brain surgery followed by whole-brain radiation therapy (WBRT: treatment that directs radiation into the brain) can improve patients’ outcome and general wellbeing. However, side effects occur and this combination does not treat cancer in the rest of the body.
For NSCLC that spreads to parts of the body other than the brain (extracranial), systemic chemotherapy (chemotherapy throughout the body) is effective. Chemotherapy drugs in the blood circulation cannot reach the brain because circulating blood and the brain are separated by tight lining of cells (blood-brain barrier). Therefore, chemotherapy is not effective for NSCLC brain metastasis. EGFR-TKIs are a group of drugs that slow down or inhibit growth of cancer cells and can improve overall survival in extracranial NSCLC. Recent research suggests that these drugs may also be useful for NSCLC brain metastasis.
Methods & findings
The authors aimed to evaluate if EGFR-TKIs are also effective treatments for NSCLC brain metastasis.
Higher doses of EGFR-TKIs are needed to treat brain tumors compared to tumors in the rest of the body. Based on several studies, increasing the dose of TKIs such as erlotinib (Tarceva) and gefitinib (Iressa) from 250 mg/day to 500 or 600 mg/day helped control NSCLC brain metastasis. Further increases were not possible due to side effects such as nausea, tiredness, and liver damage.
Data from 41 patients with NSCLC brain metastasis were analyzed to assess the effectiveness of gefitinib plus WBRT. Every patient received gefitinib and 43.9% of patients received WBRT before gefitinib. The cancer was controlled in 56% of patients who received gefitinib plus WBRT compared to 9% of patients who only received gefitinib. In another study 90 NSCLC patients received either gefitinib or gefitinib plus WBRT. More patients in the gefitinib plus WBRT had complete or partial disappearance of the tumor (64.4%) than in the gefitinib only group (26.7%) Patient survival was almost doubled after gefitinib plus WBRT (23.40 months) compared to gefitinib only (14.83 months).
In a study of 69 NSCLC patients with brain metastasis, the link between mutations (permanent change) in EGFR gene (an important protein in cellular signaling) in the lung tumor and effectiveness of erlotinib was analyzed. The tumor partially or completely disappeared in 82.4% of patients who had EGFR mutations. Patients with EGFR mutations survived for an average of 12.9 months, while patients whose EGFR status was unknown survived 5.8 months.
The bottom line
The authors concluded that EGFR-TKIs were safe and effective for NSCLC patients with EGFR mutations who have brain metastasis.
Published By :
Cancer Letters
Date :
May 23, 2014
