Clinical phase I pilot study of the alkyl lysophospholipid derivative ET-18-OCH₃ ¹

Abstract

Sixteen patients suffering from widespread malignant disease, the majority pretreated and found in poor general health, were treated in a phase I pilot study with the alkyl lysophospholipid derivative 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (E-18-OCH₃). Eleven patients were treated intravenously, and five were given oral therapy. Prolonged IV administration of 15–20 mg/kg/day at a concentration of 5 mg ET-18-OCH₃ per 1 ml 20% human serum albumin could be continued safely. The maximum-tolerated dose was either 50 mg/kg as a single injection or 20 mg/kg during daily dispensions. Grade 2–4 toxicity, as pulmonary edema and impairment of hepatic function, then occurred during daily treatment. Toxicity was reversible. Mitogen stimulation and mixed lymphocyte culture studies revealed possible immunosuppressive effects of higher doses of ET-18-OCH₃. There were no chromosomal changes in cytogenetic studies. Frequent post-mortem examinations revealed no further toxicity. IV and oral treatment showed few encouraging response data since there were two partial remissions in non-small cell lung cancers and a reduction of leukemic blasts to less than 10% in an acute myelomonocytic leukemia.