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Management of recurrent malignant pleural effusions is a common problem. At present the agent of choice is intrapleural talc, but it is not without side effects. Attention is therefore being directed toward strategies to target specific cellular mediators of the pleural inflammatory cascade. As there is fibrotic change in the pleural cavity as a result of infection, the authors of this study hypothesised that molecular mimics may be able to induce effective pleurodesis.
This phase I toxicity and dose escalation study was conducted in 14 patients with histologically-proven malignant pleural effusions. Patients were excluded if there was any sign of current infection. An indwelling pleural catheter was inserted, pleural fluid drained completely and any subsequent output recorded for 6 days. Intrapleural saline injection at day 0 served as a control. On day 7, patients received a single intrapleural injection of lipoteichoic acid T (LTA-T) according to a dose escalation schedule. From day 7 to 14, daily drainage volume was recorded and pleural fluid stored for further analysis. Recordings were made of adverse effects.
A therapeutic dosage of 750–1500 μg was identified based on detectable systemic inflammation at this dose. There was a decrease in pleural fluid production and permanent pleurodesis achieved after 1 month in 75% of eligible patients. Toxic effects were mild, there was no consistent side effect profile and the LTA-T side effect profile compared favourably with talc.
Further studies are needed, but LTA-T may provide a useful alternative to talc for pleurodesis in this setting.
▸ Rahman NM, Davies HE, Salzberg M, et al. Use of lipoteichoic acid T for pleurodesis in malignant pleural effusion: a phase I toxicity and dose-escalation study. Lancet Oncol 2008;9:946–52.