Sclerosol (Talc Intrapleural) - Clinical Pharmacology

CLINICAL PHARMACOLOGY

Mechanism of Action:

The therapeutic action of talc instilled into the pleural cavity is believed to result from induction of an inflammatory reaction. This reaction promotes adherence of the visceral to the parietal pleura, obliterating the pleural space and preventing reaccumulation of pleural fluid. The extent of talc systemically absorbed after intrapleural administration has not been adequately studied. Systemic exposure could be affected by the integrity of the visceral pleura, and therefore could be increased if talc is administered immediately following lung resection or biopsy.

CLINICAL STUDIES

The data demonstrating safety and efficacy of talc in the treatment of malignant pleural effusions are derived from the published medical literature. The following four trials were prospective, randomized studies of talc vs. a concurrent control, and provide sufficient detail for evaluation, including a clear, readily determined definition of response (no fluid reaccumulation by chest roentgenogram at one month or greater) and information allowing an analysis of all patients randomized. Talc was statistically significantly superior to the control arms in evaluable patients across the studies.

REFERENCE	TREATMENT	TUMOR	RESPONSE RATE IN EVALUABLE PTS p value: Fisher's Exact*	RESPONSE RATE IN ALL PATIENTS p value: Fisher's Exact*	MINIMUM DURATION OF RESPONSE
*p values are two-sided
Sorenson et al. Eur J Respir Dis. 1984; 65:131	Talc slurry vs Chest tube drainage	Variety	100% (9/9) vs 58% (7/12) p=0.022	64% (9/14) vs 41% (7/17) p=0.285	3 months
Fentiman et al. Eur J Cancer Clin Oncol 1986; 22:1079	Talc poudrage vs Tetracycline solution	Breast	92% (11/12) vs 48% (10/21) p=0.022	61% (11/18) vs 43% (10/23) p=0.345	12 months
Fentiman et al. Cancer 1983; 52:737	Talc poudrage vs Mustine solution	Breast	90% (18/20) vs 53% (9/17) p=0.023	78% (18/23) vs 39% (9/23) p=0.016	6 months
Hamed et al. Br. J. Surg 1989; 76:1266	Talc poudrage vs Bleomycin solution	Breast	100% (10/10 procedures) vs 33% (5/15 procedures) p=0.001	(unclear; results reported as procedures, not patients)	≥1 months

In other studies, greater than 1000 patients with malignant pleural effusions have been reported (with varying degrees of detail and durations of response) to have had successful pleurodesis with talc.