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Phase I Trial of Intravenously Administered Endotoxin (Salmonella abortus equi) in Cancer Patients¹

Medizinische Klinik I der Albert-Ludwigs-Universität [R. E., A. M.], and Max Planck Institut für Immunbiologie [C. G.], D-7800 Freiburg, Federal Republic of Germany

We report a phase I study in cancer patients being treated with i.v. bolus injections of highly purified lipopolysaccharide (LPS) Salmonella abortus equi. Twenty-four patients with disseminated cancer received escalating doses of LPS at 2-week intervals. Dose escalation was performed in six dose levels treating 3–6 patients at each level. Dose levels 1 and 2 consisted of 0.15 and 0.3 ng/kg, respectively. Further dose escalation up to 5.0 ng/kg was enabled by pretreatment with ibuprofen, which attenuated the constitutional side effects of LPS. The maximum tolerated dose was 4.0 ng/kg with dose-limiting toxicity being World Health Organization grade III hepatic toxicity. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes in a marked different pattern. Endogenous cytokine release occurred in an LPS dose-dependent manner as measured by tumor necrosis factor-, interleukin-6, and macrophage colony-stimulating factor serum levels. Moderate antitumor activity in colorectal cancer was observed in the case of 2 patients. Phase II trials of LPS are currently in progress.

¹ Supported by Bundesminister für Forschung und Technologie of the Federal Republic of Germany (Grant 01KB8802).

² To whom requests for reprints should be addressed, at Medizinische Universitätsklinik, Hugstetterstr. 55, D-7800 Freiburg, Federal Republic of Germany.

Received 11/14/90. Accepted 3/ 7/91.

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