Gemcitabine-Cisplatin, Gemcitabine-Carboplatin
An Australian study group evaluated the doublet gemcitabine-cisplatin in 21 patients presenting with advanced Malignant Pleural Mesothelioma (MPM) (Byrne et al, 1999). The subjects received gemcitabine at 1000 mg m-2 on day 1, 8 and 15 and cisplatin at 100 mg m-2 on day 1 of a 28-day cycle. This combination chemotherapy produced an encouraging response rate of 47.6% and an overall survival of 41 weeks. Furthermore, nine of 10 responding patients experienced significant relief of chest pain and dyspnoea. Subsequently, a multicentre study was initiated, evaluating the same chemotherapy regimen in 53 Malignant Pleural Mesothelioma (MPM) patients (Novak et al, 2002). A response rate of 33% was achieved and the median survival time was 11.2 months. Response to treatment was accompanied by significantly improved global quality of life and respiratory function.
Contrary to the Australian trials, however, only four (15%) of 22 assessable subjects experienced a partial response within a European multicentre phase II study (Van Haarst et al, 2000) of gemcitabine at 1250 mg m-2 on days 1 and 8, in addition to cisplatin at 80 mg m-2 on day 1. The discrepancy between these studies may possibly result from the different treatment schedules, patient selection criteria and methodology applied in treatment evaluation.
In turn, Aversa et al, (1998) on evaluated the activity of the gemcitabine-carboplatin combination. A total of 20 patients were given gemcitabine at 1000 mg m-2 on days 1, 8 and 15 and carboplatin (AUC=5) on day 1, every 28 days for a median of 4.5 cycles. In 18 assessable subjects, a response rate of 16% and an 8.6-month median survival rate was achieved.
Recently, investigators at the University of Chicago have initiated a multicenter, randomised phase II trial of cisplatin-gemcitabine and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab, which has shown preliminary evidence of activity in Malignant Pleural Mesothelioma (MPM).