Activity and tolerability of cisplatin (CDDP) and fotemustine (FTM) in non-small cell lung cancer (NSCLC) patients (PTS) with brain metastases (BM): A multicentric phase II study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)

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e19085 Background: More than 50% of BM occurs in advanced NSCLC. In most cases BM are multiple and their standard therapy is whole-brain radiation therapy (WBRT) since the role of systemic therapies for is still a matter for investigation due to concerns on the drugs ability cross the blood brain barrier (BBB). FTM is a nitrosourea able to cross BBB and CDDP remains the backbone for medical treatment of NSCLC. Methods: Pts with advanced NSCLC, ECOG PS 0–1 and multiple BM were treated with 2 cycles of FTM 80 mg/m2 d1,8 and CDDP 80 mg/m2 d1 q3 wks followed by WBRT 30 Gy/3 Gy daily; radiological response using Recist Criteria were analysed before WBRT to assess the role of FTM/CDDP both for cranial and extracranial disease. Pts with disease control (DC) received further CT up to 6 cycles. Barthel ADL Index was administered every 2 cycles. The trial has a two step design according to Simon: 29 pts were required to verify if FTM/CDDP was able to achieve a >25% response rate both for cranial and extracranial disease (step 1), and if this was true further pts had to be enrolled up to 81 pts (step 2). Results: At first evaluation 4/29 pts were excluded from the study (2 not treated/ 1 never included/1 not eligible). Therefore patient's demographics were: median age 61 (range 48–73), M/F 16/9, adeno 11, squamous 5, large cell 2, nos 7; PS 0/1: 1/14, Barthel Index median value at the starting point 20 (13–20). Overall 3/25 (12%) partial responses were observed with 9 (36%) stable diseases and 13 (52%) progressions of disease. These data did not satisfy the pre-planned hypothesis and the study was stopped at the first step. Before WBRT after the first 2 CT cycles 13/25 pts (48%) had a systemic DC in contrast with 15/25 pts (60%) with brain tumour DC. WBRT seemed not useful to further modify the results of CT. CT was relatively well tolerated with asthenia as the most relevant specific toxicity while the hematological toxicity was mild. Conclusions: CDDP and FTM combined with WBRT could represent a therapeutic option for patients with NSCLC even if the global therapeutic index was not satisfactory. Further studies evaluating the combination of systemic treatments with WBRT are warranted. No significant financial relationships to disclose.