ZD0473 treatment in lung cancer: An overview of the clinical trial results

Three open-label, non-comparative, multicentre Phase II trials have examined the efficacy and tolerability of ZD0473 as first-and second-line therapy in non-small-cell lung cancer (NSCLC) patients and second-line therapy in small-cell lung cancer (SCLC) patients. Patients with second-line NSCLC or SCLC were evaluated as either platinum-sensitive or -resistant, based upon their time to relapse/progression after platinum-based therapy. First-line NSCLC patients (n = 18) received a total of 60 treatment cycles (median number per patient 2.5) whilst second-line NSCLC (n = 50) and SCLC (n = 48) patients both received a total of 127 treatment cycles (median number per patient 2.0). Grade 3/4 anaemia, neutropenia and thrombocytopenia was observed in: 38.8%, 22.2% and 27.7% of first-line NSCLC patients; 12.0%, 24.0% and 50% of second-line NSCLC patients; and 10.4%, 25.0% and 47.9% of second-line SCLC patients, respectively. The most common grade 3/4 non-haematological toxicities in all three trials were lethargy and dyspnoea. No clinically significant oto-, nephro- or neurotoxicity was observed. The first-line treatment of NSCLC produced an overall response rate (OR) of 6.3%. No OR was seen after second-line treatment of NSCLC, while ORs of 15.4% and 8.3% were seen in the platinum-resistant and -sensitive second-line SCLC patients, respectively.