Background: Brain metastases (BM) represent one of the most common challenges related to non-small cell lung cancer (NSCLC), with evolving treatment strategies. We have conducted a phase II clinical trial in a Chinese population to evaluate concomitant treatment with whole brain radiotherapy (WBRT) and Gefitinib in patients with BM from NSCLC. The purpose of this study is to report the efficacy and toxicity of this treatment, and assess its impact on patient Quality of Life (QoL) and survival post-treatment.
Patients and methods: Between October 2005 and January 2007, 21 patients were enrolled and received 40Gy/20f/4w WBRT. Gefitinib was administrated orally at a dosage of 250mg/day during the radiation course and was continued for each 28-day treatment cycle until progression of the disease, unacceptable toxicity, or withdrawal of consent. The primary end point of the study was tumor response and QoL. The secondary end points were toxicity and survival. Objective response rate according to the RECIST criteria was recorded. Health-related QoL was measured using FACT-Br (V4.0) and toxicity was evaluated and recorded using the NCI Common Toxicity Criteria. The Kaplan-Meier method was used to evaluate patient survival. Univariate analysis of patient characteristics and tumor responses was conducted using the Chi-square and Fisher's exact test.
Results: Four (19%) and 13 patients (62%) had a complete and partial response respectively, while 3 patients disease remained stable and 1 patient had progression of the disease. The overall response rate (81%, 95% confidence interval (CI): 58-95%) exceeded the goal per study design. The median progression-free survival and overall survival were 10.0 months (95% CI: 7.5-12.5 months) and 13.0 months (95% CI: 8.2-17.8 months), respectively. The most frequent toxicities included rash (86%) and diarrhea (43%), with only 3 patients developing a grade III diarrhea. Other grade II or higher toxicities occurring in about 50% of patients included nausea, vomiting, headache, and fatigue. Most side effects were grade II and well tolerated by supportive care. Gender and cigarettes/year were predictive factors for the responses found in univariate analysis. All domains of QoL were significantly improved following treatment.
Conclusion: Our data suggests that concomitant treatment was well tolerated, with promising activity and a significant improvement of QoL in a Chinese population with brain metastases from NSCLC. Although the data presented herewithin appears promising, more data from randomized trials are needed to further validate this regimen of WBRT/Gefitinib.