Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma

The role of second-line therapy in patients with malignant pleural mesothelioma (MPM) progressing after first-line pemetrexed-based chemotherapy (PBC) is currently undefined. Recent case series have suggested a possible role of re-treatment with PBC. In this observational study, the activity and safety of this therapeutic option was assessed in a consecutive series of cases. Patients with complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 3 months after first-line PBC were retreated with PBC, either as second-line (2L) or further-line (>2L) therapy. Descriptive analyses of progression-free survival (PFS), overall survival (OS), response rate and toxicity are reported. Between October 2004 and July 2009, 31 patients (21 males and 10 females) received re-treatment with PBC as 2L (18 patients) or beyond 2L therapy (13 patients). Median age was 65 years (range 37-81). Fifteen patients were re-treated with pemetrexed alone, and 16 with a pemetrexed/platinum combination. An objective response was achieved in 6 patients (one CR and 5 PRs), for a response rate of 19%. Nine patients (29%) had SD after treatment. Overall, the disease control rate (DCR) was 48%. Median PFS and overall survival (OS) after re-treatment with PBC were 3.8 months and 10.5 months, respectively. PFS and OS after re-treatment with PBC were correlated with PFS achieved after first-line PBC (FL-PFS). Patients with a FL-PFS >12 months had a median PFS after re-treatment of 5.5 months, while patients with a FL-PFS ≤12 months had a median PFS after re-treatment of 2.5 months; no patient in this group was progression-free at 1 year. Toxicity was mild, with grade 3 or 4 hematological toxicity occurring in 9.7% of patients. In conclusion, re-treatment with PBC should be considered as second-line therapy in MPM patients achieving a durable (>12 months) disease control with first-line PBC. Further prospective evaluation of this therapeutic option is warranted.