Frontline Cytotoxic Chemotherapy (CTx) for Newly Diagnosed Non–Small-Cell Lung Cancer (NSCLC) Patients Presenting with Brain Metastasis Compared to Whole-Brain Radiotherapy (WBRT): Result of a Randomized Pilot Study

Background Whole-brain radiation therapy (WBRT) followed by chemotherapy is commonly used for patients with non–small-cell lung cancer (NSCLC) with brain metastasis. However, when neurologic symptoms or signs are absent or controlled by supportive care, chemotherapy could be a choice of treatment. We conducted a randomized pilot trial of frirst-line chemotherapy compared with WBRT in this clinical setting of whether first-line chemotherapy was feasible and whether its efficacy and toxicity profiles, as well as quality of life and survival outcome, were affected by the time of WBRT. Patients and Methods The eligibility criteria were as follows: pathologically confirmed NSCLC, stage IV with brain metastasis at first diagnosis, age 18-75 years, Eastern Cooperative Oncology Group performance status (PS) 0-2, and adequate organ functions. After stratification according to PS (Eastern Cooperative Oncology Group 0/1 vs. 2), the number of intracranial metastases ( 2 and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks, up to 6 cycles. Whole-brain radiation therapy consisted of 10 fractions of 30 Gy for 12 days. We assessed tumor response, toxicity profile, and quality of life according to World Health Organization response criteria, National Cancer Institute Common Toxicity Criteria, and European Organization for Research and Treatment of Cancer C-30/ LC-13 questionnaires, respectively. Results Between August 2002 and November 2005, 48 patients were enrolled. All 25 patients in arm A received chemotherapy and WBRT, whereas 4 of 23 patients (17%) in arm B could not receive chemotherapy because deterioration of PS or death during or immediately after WBRT. Intracranial tumor responses to chemotherapy in arm A were closely correlated with extracranial responses (k = 0.82). There were no statistically significant differences in overall response rate (28% vs. 43%), time to progression (6.4 months vs. 6.3 months) and overall survival (9.1 months vs. 9.9 months). However, grade 3/4 neutropenia occurred more frequently in arm B (79% vs. 40%; P = 0.014). Cognitive function deteriorated during first-line chemotherapy, whereas it did not deteriorate further during chemotherapy after WBRT, but the score had already lowered after WBRT. Conclusion First-line chemotherapy can be an appropriate treatment when neurologic symptoms or signs are absent or controlled by supportive care. The timing and the real need for WBRT should be defined in further trials.