Phase I study of liposomal annamycin |
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Authors: | Daniel J Booser Roman Perez-Soler Paul Cossum Laura Esparza-Guerra Qing-Ping Wu Yiyu Zou Waldemar Priebe Gabriel N Hortobagyi |
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Institution: | (1) Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 56, Houston, Texas 77030-4095, USA Tel.: +1-713-7922817; Fax: +1-713-7944385, US;(2) Department of Thoracic Head and Neck Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA, US;(3) Department of Immunobiology and Drug Carriers, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA, US;(4) The University of Texas M.D. Anderson Cancer Center, Houston, Texas, US;(5) Aronex Pharmaceuticals, Inc., The Woodlands, Texas, USA, US |
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Abstract: | Annamycin is a highly lipophilic anthracycline with the ability to bypass the MDR-1 mechanism of cellular drug resistance.
In this phase I study, annamycin entrapped in liposomes was administered by a 1- to 2-h intravenous infusion at 3-week intervals.
Thirty-six patients with relapsed solid tumors were treated and 109 courses were administered at doses ranging from 3 to 240 mg/m2. The dose-limiting toxicity was thrombocytopenia. Five patients had a probable allergic reaction, requiring discontinuation
of treatment in one. Treatment was well tolerated otherwise. No cardiac toxicity was seen on endomyocardial biopsy of four
patients studied. There was limited gastrointestinal toxicity and no alopecia. No objective tumor responses were observed.
Pharmacokinetic studies at 24, 120 and 240 mg/m2 showed a biexponential plasma concentration-versus-time profile. There was a linear relationship between the dose and the
maximal plasma concentration with relatively constant plasma clearance values. The maximum tolerated dose (MTD) for liposomal
annamycin defined in this study is 210 mg/m2. Because of a subsequent change in the formulation of the drug, future studies will use 190 mg/m2 as the MTD.
Received: 28 December 1999 / Accepted: 29 June 2000 |
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Keywords: | Anthracycline Phase I study Pharmacokinetics |
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