Phase I study of iv mycobacterial cell wall skeleton and cell wall skeleton combined with trehalose dimycolate.
A phase I study to determine the toxicity and immunologic effects of iv administered aqueous suspensions of mycobacterial cell wall skeleton (CWS) and CWS combined with trehalose dimycolate (TDM) was performed. A total of 26 patients received suspensions of either CWS or CWS/TDM given iv every 1 or 2 weeks in set doses of either 100, 250, 500, or 1000 micrograms/m2. The major dose-limiting side effects for both preparations were fever and chills at a dose of 1 mg/m2. This was more severe with the combined CWS/TDM. There was no renal or pulmonary toxicity. There was evidence of hepatic toxicity, with increases in the alkaline phosphatase and gamma glutamyl transferase, especially with high doses of CWS/TDM. Both the CWS and CWS/TDM groups had an increase in their wbc count. In the patients receiving CWS alone, there was a decrease in the peripheral blood monocytes. In the CWS/TDM group, there was an increase in the serum lysozyme, suggesting macrophage activation. No antitumor effect was seen in this phase I study. Aqueous suspensions of CWS and CWS/TDM can be administered safely iv over a period of time, with evidence of an effect on hematologic parameters.
D000818:Animals; D001772:Blood Cell Count; D001798:Blood Proteins / Q000032:analysis; D002473:Cell Wall / Q000276:immunology; D003311:Cord Factors / Q000008:administration & dosage*; D004341:Drug Evaluation; D006017:Glycolipids / Q000008:administration & dosage*; D006168:Guinea Pigs; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008168:Lung / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology*; D012882:Skin Tests
D001798:Blood Proteins; D003311:Cord Factors; D006017:Glycolipids