A randomised trial in malignant mesothelioma (M) of early (E) versus delayed (D) chemotherapy in symptomatically stable patients: The MED trial

Background: Prior phase II trials have demonstrated the therapeutic activity of cytotoxic chemotherapy in mesothelioma. Currently there are few randomised data assessing the role of chemotherapy versus best supportive care (BSC) in the management of patients with stable symptoms after control of any pleural effusion. A policy of observation is often adopted over initial use of chemotherapy. In this prospective randomised trial we assess the use of early versus delayed cytotoxic therapy. The study opened in 1998, and closed in view of a competing national study (MSO 1) in 2003. Methods: Eligible patients had a performance status ≤2, life expectancy >3 months and had stable symptoms for at least 4 weeks prior to randomisation. Patients were randomised to receive immediate chemotherapy or initial BSC with the addition of chemotherapy at time of symptomatic progression. All patients received the same platinum-based chemotherapy regimen, MVP [mitomycin C 8 mg/m² cycles 1, 2, 4 and 6, vinblastine 6 mg/m², maximum 10 mg, and cisplatin 50 mg/m² (or carboplatin AUC 5)], every 3 weeks for up to six cycles. Results: A total of 43 patients were recruited, of which 21 were randomised to the early treatment group and 22 to the delayed treatment group. The median ages were 59 years (range 50-78) and 67 years (range 48-75), respectively (P = 0.1); other baseline parameters were well matched between the two groups. All 21 patients in the early group received chemotherapy versus 17 patients in the delayed group. Median time to symptomatic progression was 25 weeks in the early group compared with 11 weeks for the delayed group (P = 0.1). Median survival was 14 months (1-year survival 66%) for the early group compared with 10 months (1-year survival 36%) for the delayed group (P = 0.1). Quality of life was in general better maintained for early treatment and the health resources use was similar in both arms. Conclusions: In this patient group, presenting with stable symptoms after control of pleural effusion, the early use of chemotherapy provided an extended period of symptom control, and in this small trial a trend to survival advantage.