Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma.

Purpose: To investigate the toxicity and effectiveness of pemetrexed maintenance therapy (PMT) in patients with malignant pleural mesothelioma (MPM).

Patients And Methods: Eligible were patients with histologically proven advanced MPM, WHO PS 0-2 and adequate hematological, renal and hepatic function in whom during 6 courses of pemetrexed containing induction therapy no disease progression was observed. PMT, 500 mg/m intravenously on day 1 every 3 weeks, was continued until disease progression, unacceptable toxicity, or if continuation was considered to be not in the patient's best interest. Written informed consent was obtained from all patients.

Results: Of the 27 patients who received induction therapy, 13 were treated with PMT. The median number of PMT courses was 4 (range = 2 to 14). No grade 4 toxicity was observed. Grade 3 neutropenia, leucopenia and anemia occurred 15%, 8% and 8%, respectively. The only non-hematological grade 3 toxicity during PMT was fatigue (15%). During PMT creatinine clearance decreased from 88 (+/-21) ml/min to 77 (+/-26) ml/min (p < 0.05). The reason to stop PMT was disease progression (69%), toxicity (23%) and in patient's best interest (8%). During PMT 23% of the patients with stable disease after induction therapy achieved a partial response. Time to progression and overall survival were 3.4 and 6.0 months versus 8.5 and 17.9 months, respectively (p < 0.0001).

Conclusions: PMT in MPM patients is non-toxic, well tolerated and although promising effects on TTP and OS are demonstrated, the effectiveness of PMT should be further explored in a prospective randomized clinical trial.