Phase I clinical trial of nimotuzumab in combination with concurrent chemo-radiotherapy in patients diagnosed with locally advanced non-small cell lung cancer

Objective To observe the feasibility of nimotuzumab in combination with concurrent chemo-radiotherapy in locally-advanced non-small cell lung cancer (NSCLC).Methods From 2011 to 2012,Untreated stage ⅢA/ⅢB NSCLC patients were chosen and divided into three weekly dose level of nimotuzumab:100 mg,200 mg and 400 mg,3-6 cases per group.If one of the first three patients experienced DLT,three additional patients were recruited to that dose level.If DLTs were observed in 50％ patients in any cohort,dose escalation was stopped and that dose was designated the maximum tolerated dose.Intensity-modulated radiotherapy (IMRT) was taken,with total dose of 60-66 Gy in 30-33 fractions.Concurrent cisplantin and etoposide chemotherapy were performed.After concurrent treatment,consolidation weekly nimotuzumab treatment was performed until 16 weeks or disease progression observed.Assessment of efficacy and safety were performed via RECIST and CTC AE V3.0,respectively,maximum change in tumor volume and survival were calculated.Results Totally 9 cases enrolled.All three dose level were well tolerated,no dose-limiting toxicity observed.The most commonly reported severe adverse events were grade 3 hematological,including leucopenia (66％),neutropenia (66％),anemia (11％),and thrombocytopenia (22％).Most common non-hematological toxicity are esophagitis,grade 1 (44％) or 2(22％),grade 1 radiation pneumonitis (44％),and grade 1 nausea/vomiting (44％).Mean total tumor volume decrease was 88％.With median survival of 26.4 months,the total 1 year and 2 year overall survival,disease free survival and progression free survival were 78％ and 67％,56％ and 44％,78％ and 56％,respectively.Conclusion Weekly 100 mg,200 mg and 400 mg nimotuzumab in combination with concurrent chemoradiotherapy can be well tolerated in locally advanced non-small cell lung cancer. Key words: Lung neoplasms/chemoradiotherapy;  Nimotuzumab ;  Clincal study