Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie (GFPC) Protocol 95-1

Purpose: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence sur vival in patients with non-small-cell lung cancer (NSCLC) and concurrent br ain metastasis. Patients and methods: One hundred seventy-six patients with brain metastasi s from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1, 8, 15, 22. Cycles were repeated every fo ur weeks. Evaluation of response was performed after two, four or six cycle s. After two cycles, chemotherapy was administered to the responders to a m aximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/ 12 days and delayed corticosteroids, (arm A) for the intracranial nonrespon ders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B ). Results: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-s ix and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 1 7 partial responses) after two cycles of chemotherapy alone (arm A) and a 2 0% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). T he intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 we eks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of a rm B patients. There were thirteen treatment-related deaths (six in arm A a nd seven in arm B). There was no difference between the arms for haematolog ical and neuro-toxicities. Conclusions: These results confirm the efficacy of chemotherapy in brain me tastases of NSCLC and suggest that the timing (early or delayed) of WBRT di d not influence survival of NSCLC with brain metastasis treated with concur rent chemotherapy.