An improved method of delivering a sclerosing agent for the treatment of malignant pleural effusion

BMC Cancer. 2019 Jun 24;19(1):614. doi: 10.1186/s12885-019-5777-z.

Abstract

Background: Malignant pleural effusion (MPE) is a devastating sequela associated with cancer. Talc pleurodesis is a common treatment strategy for MPE but has been estimated to be unsuccessful in up to 20-50% of patients. Clinical failure of talc pleurodesis is thought to be due to poor dispersion. This monograph reports the development of a foam delivery system designed to more effectively coat the pleural cavity.

Methods: C57BL/6 mice were injected with Lewis lung carcinoma (LL/2) cells intrapleurally to induce MPE. The mice then received either normal saline (NS) control, foam control (F), talc slurry (TS, 2 mg/g) or talc foam (TF, 2 mg/g). Airspace volume was evaluated by CT, lungs/pleura were collected, and percent fibrosis was determined.

Results: The TF group had significantly better survival than the TS group (21 vs 13.5 days, p < 0.0001). The average effusion volume was less in the talc groups compared to the control group (140 vs 628 μL, p < 0.001). TF induced significant lung fibrosis (p < 0.01), similar to TS. On CT, TF significantly (p < 0.05) reduced loss of right lung volume (by 30-40%) compared to the control group. This was not seen with TS (p > 0.05).

Conclusions: This report describes using a novel talc foam delivery system for the treatment of MPE. In the LL/2 model, mice treated with the TF had better survival outcomes and less reduction of lung volume than mice treated with the standard of care TS. These data provide support for translational efforts to move talc foam from animal models into clinical trials.

Keywords: Lung cancer; Malignant pleural effusion; Metastatic cancer; Mouse model; Pleurodesis; Sclerosing agent; Talc; Thermosensitive hydrogel.

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / complications
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Female
  • Fibrosis / diagnosis
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Lung / pathology
  • Lung Volume Measurements
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pleura / pathology
  • Pleural Effusion, Malignant / etiology
  • Pleural Effusion, Malignant / therapy*
  • Pleurodesis / methods*
  • Sclerosing Solutions / administration & dosage
  • Sclerosing Solutions / therapeutic use*
  • Talc / administration & dosage
  • Talc / therapeutic use*
  • Transition Temperature
  • Treatment Outcome

Substances

  • Sclerosing Solutions
  • Talc
  • Hydrogel, Polyethylene Glycol Dimethacrylate