Pulmonary function in patients with trophoblastic disease treated with low-dose methotrexate

The Sheffield Trophoblastic Disease Centre treats about 25 patients with persistent trophoblastic disease each year. A total of 75% of patients are classified as low risk according to the Charing Cross Hospital prognostic scoring system and receive methotrexate (MTX) 50 mg, i.m., on days 1, 3, 5, 7 with folinic acid 7.5 mg orally 24 h after each methotrexate injection. There is a 7-day rest between treatment cycles. Remission is achieved in 85% of cases. Approximately 20% of patients experienced pleuritic chest pain and dyspnoea. We have evaluated prospectively lung function in 16 low-risk patients receiving methotrexate. All patients had pulmonary function tests [spirometry-forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and transfer factor - TLCO, kCO] performed before and after completed treatment. A mean of 7.5 cycles of MTX were administered (range 4-11). There was a significant reduction in the mean TLCO (mean pre/post 8.15/7.38 mmol min-1 kPa-1, P = 0.01), but there were no other statistically significant changes. Three patients experienced respiratory symptoms and were found to have a 39%, 28%, and 11% reduction in TLCO from baseline, improving on follow up to pretreatment levels. Low-dose MTX is an effective therapy but may cause troublesome pulmonary toxicity.