Innovative sequence of docetaxel–gemcitabine based on preclinical data in the treatment of advanced non small cell lung cancer: a phase I study

Based on our previous preclinical data, a phase I study was designed to investigate the tolerability of a novel sequence, docetaxel (DOC)-gemcitabine (GEM), in the treatment of non small cell lung cancer (NSCLC). Preclinical study: We evaluated the cytotoxicity of DOC and GEM on NSCLC cell lines and assessed the type of interaction between drug activities following different treatment schemes. Clinical study: Fifteen patients with stage IIIB-IV NSCLC received DOC (day 1) and GEM (days 3 and 8) every 21 days. Dose escalation of both agents was used to identify the maximum tolerated dose. The study was closed at the fifth dose level due to the occurrence of three dose-limiting toxicities: grade 4 febrile neutropoenia, persistent grade 2 fever and grade 3 diarrhoea. The most frequent toxicity was neutropoenia. Non haematological toxicities were diarrhoea, nausea and vomiting, mucositis and alopoecia. Of the 14 evaluable patients, 1 complete response, 4 partial responses, 4 stable diseases and 5 disease progressions were observed. Based on the results of the present study, a phase II trial is ongoing using the fourth dose levels.