PHASE-I STUDY OF RP 49532A, A NEW PROTEIN-SYNTHESIS INHIBITOR, IN PATIENTS WITH ADVANCED REFRACTORY SOLID TUMORS

Giroline (RP 49532A) is a new protein-synthesis Inhibitor with broad antitumor activity in experimental models. In the present phase I study, Giroline was given by 24-h i.v. infusion every 3 weeks at doses ranging from 3 to 15 mg/m(2) to 12 patients with advanced refractory solid tumors. The dose-limiting toxic effects were delayed hypotension and severe asthenia. The maximum tolerated dose (MTD) was 15 mg/m(2). Transient nausea and vomiting during infusion were reported at all dose levels. Mild reversible prolongation of prothrombin time and activated partial thromboplastin time was observed in most patients at dose levels above 3 mg/m(2). No antitumor activity was observed. The toxicity profile of Giroline precludes further evaluation in cancer patients.