Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy whose incidence is increasing throughout the world. The diffuse spreading growth of this neoplasm makes surgery difficult and hence an option for only a minority of the patients (Treasure and Sedrakyan, 2004). The treatment options for the majority of patients are best supportive care and palliative chemotherapy (Ceresoli et al, 2006a, 2006b). Chemotherapy for MPM is challenging, although several cytotoxic agents have been tested and the rates of objective tumour response have ranged from 10 to 30% with monotherapy (Tomek and Manegold, 2004). Cisplatin and carboplatin are both active and thus usually included in the most used combination chemotherapy regimens for MPM (Sorensen, 2008). Pemetrexed is a multitargeted antifolate with a 14% response rate as a single agent in chemotherapy-naive MPM patients (Scagliotti et al, 2003). A recent randomised trial showed that combination chemotherapy with pemetrexed and cisplatin was superior to cisplatin single-agent treatment with respect to both time to progression and overall survival (Vogelzang et al, 2003). Raltitrexed is another antifolate tested in combination with cisplatin against cisplatin alone in a randomised trial (van Meerbeeck et al, 2005). The combination was superior compared to cisplatin alone with respect to time to progression but not with respect to overall survival. A recent randomised study compared active symptom control (ASC) alone to ASC plus vinorelbine and to ASC plus mitomycin plus vinblastine plus Cisplatin (Muers et al, 2007). The impact of chemotherapy on symptom control and quality of life have been evaluated in both of these randomised trials, pointing towards an improvement with respect to dyspnoea and stabilisation with respect to other parameters (Boyer et al, 2003; Bottomley et al, 2006). The activity of the chemotherapy is still modest, and hence novel agents need to be evaluated for use in combination chemotherapy regimens for improvement of outcome (Green et al, 2007). A large number of single agents have been tested for activity in MPM (Berghmans et al, 2002; Ellis et al, 2006; Sorensen, 2008). The third generation vinca alkaloid vinorelbine has attracted interest in a phase II trial using vinorelbine 30 mg m−2 i.v. weekly (Steele et al, 2000). A cycle consisted of 6 weekly injections and the median number of injections was 12. The intention-to-treat response rate among 29 chemotherapy-naive MPM patients was 24% (95% confidence level 10–44%) and the fraction of patients alive 1 year from time of first treatment was 41%, which ranks vinorelbine among the most active agents in MPM. Toxicity was modest. On the basis of these results, it seems interesting and feasible to evaluate the activity of vinorelbine together with cisplatin. The feasibility and tolerability of this doublet is already very well known from its use in non-small cell lung cancer (NSCLC) in which it is among the most active regimens. Both the South West Oncology Group (SWOG) and the French group have published their data on activity and toxicity in NSCLC using cisplatin 100 mg m−2 every 4 weeks together with weekly i.v. vinorelbine 25 mg m−2 (Wozniak et al, 1998) or cisplatin 120 mg m−2 every 4–6 weeks together with weekly i.v. vinorelbine 30 mg m−2 (LeChevalier et al, 1994). Accordingly, the purpose of this study was to evaluate this regimen cisplatin and vinorelbine for its activity as first-line treatment in MPM using the regimen by SWOG.