Phase I study of intravenous mycobacterial cell wall skeleton and trehalose dimycolate attached to oil droplets.

The toxic, clinical, and immunological effects of suspensions of mycobacterial cell wall skeleton (CWS) and trehalose dimycolate (TDM) attached to oil droplets and given intravenously in doses of 100-2,000 micrograms/m2 (CWS) every 1 or 2 weeks was investigated in this Phase I study. The major limiting side effects were fever and chills at a dose of 2 mg/m2 body surface area. There was no significant hematopoietic, renal, hepatic, or pulmonary toxicity. Evaluation of changes in the white cell count and lymphocyte and monocyte populations and function showed an increase in the white blood count, an increase in the number of T cells, and a decrease in blood monocytes. Measurements of lymphocyte blastogenesis, monocyte suppressor activity, and monocyte cytostasis showed no consistent changes. Intravenous therapy with oil/CWS/TDM was associated with complete regression of a bronchial squamous cell carcinoma in one of three patients receiving 2 mg/m2 weekly. Subsequent Phase II studies can be conducted at a weekly dose of 1-2 mg/m2.