Abstract
Gemcitabine/cisplatin is among the most widely used regimens in Europe for first-line treatment of non-small cell lung cancer (NSCLC). Problems with cisplatin use in this setting include significant nonhematologic toxicity and difficulty of use in outpatients.
Carboplatin constitutes a reasonable alternative to cisplatin in this combination, since it shows synergy with gemcitabine in vitro, is easier to use in ambulatory patients, and has a better nonhematologic toxicity profile. Studies of gemcitabine/cisplatin on a 28-day schedule (gemcitabine on days 1, 8, 15 and carboplatin on day 1) generally indicate excessive thrombocytopenia.
Use of a 21-day schedule (e.g. gemcitabine on days 1 and 8, carboplatin on day 1) is associated with reduced toxicity and comparable efficacy. Results of one randomized phase II study suggest reduced toxicity and reduced objective response rate with gemcitabine/carboplatin versus gemcitabine/cisplatin.
We are currently conducting a phase III comparison of gemcitabine 1200 mg/m(2) on days 1 and 8 plus carboplatin at an area under the curve of 5 mg/ml/min on day I versus gemcitabine at the same dose plus cisplatin 80 mg/m(2) on day 1 every 21 days in chemotherapy-naive patients with stage IIIB/IV NSCLC; interim analysis indicates comparable response rates (47 and 48%). A better understanding of the relative toxicities of these regimens should be provided by the final results of this trial