Gemcitabine and carboplatin regimens in advanced non-small-cell lung cancer: focus on randomized phase III trials

In the past decade unequivocal evidence regarding the benefit of platinum-based chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has emerged. Several regimens consisting of either cisplatin or carboplatin combined with agents such as paclitaxel, docetaxel, gemcitabine, vinorelbine, or irinotecan have demonstrated superiority over older combinations or single-agent platinums. These regimens have roughly equivalent activity in terms of response and survival. The major differences have been in terms of toxicities and expense. Gemcitabine/carboplatin is a combination with clear activity in advanced disease and excellent tolerability. Unlike taxane-based therapy, there is minimal neuropathy and little alopecia. For registration purposes, gemcitabine was initially combined with cisplatin. Regimens combining gemcitabine with carboplatin reported a similar rate of myelotoxicity (primarily thrombocytopenia) as gemcitabine/cisplatin. The observation that a 21-day schedule in which carboplatin is administered on day 1 and gemcitabine on days 1 and 8 could substantially reduce this toxicity provided a preferred schedule for administration. The major factor limiting acceptance of this regimen was the absence of phase III data. This year a number of phase III trials were presented, which coupled with the results of large, multicenter phase II studies (including one from a US cooperative group), has now established gemcitabine/carboplatin as a standard regimen for the treatment of advanced NSCLC. Its excellent toxicity profile has also led several groups to utilize the regimen as a platform for combination with newer drugs.