PHASE-I AND PHARMACOLOGICAL STUDY OF ACIVICIN BY 24-HOUR CONTINUOUS INFUSION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (9) , 3892-3895
Abstract
A Phase I trial of acivicin [L-(.alpha.S,5S)-.alpha.-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid] was performed on an escalating-dosage 24-h continuous i.v. infusion schedule. Thirty-one patients received 77 courses of treatment, and all but one were evaluable for toxicity. Pharmacological monitoring in selected patients demonstrated that peak plasma levels correlated with dose. Postinfusion half-life (t1/2.beta.) was 6-9 h and urinary recovery of the administered dose was 14 to 19% as unchanged drug during the 24-h infusion. Hematological and gastrointestinal toxicities were variable and not dose related. In contrast, neurotoxicity characterized by lethargy, fatigue, confusion, disorientation, hallucinations, nightmares and truncal ataxia was dose limiting and related to plasma drug levels. A minimal antitumor response was observed in a patient with colorectal carcinoma, and a partial response occurred in a patient with liver metastases from gastric carcinoma. The recommended dose for Phase II trial by 24-h infusion is 160 mg/m2.

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