Phase I Study of Annamycin, a Novel
Liposomal Anthracycline, in Patients with Relapsed/Refractory Acute Myeloid and
ASCO Annual Meeting
Proc Am Soc Clin Oncol 20: 2001 (abstr
Andreeff, Francis Giles, Steven Kornblau, Marina Konopleva, Clinton Leysath, C.
Ellen Jackson, Kimberly Edwards, Bruce Ross, Marion Faldas, Anthony H Williams, Elihu Estey, Hagop Kantarjan,
University of Texas/M.D. Anderson Cancer Center, Houston, TX; Aronex
Pharmaceuticals, Inc., The Woodlands, TX.
Twenty-one patients with
relapsed/refractory AML (n=18) or ALL (n=3) were enrolled on a dose-finding protocol
using annamycin, a novel anthracycline developed to overcome multidrug
resistance (MDR). Annamycin is delivered by liposomes and has not shown
cardiotoxicity in preclinical studies. We have previously demonstrated that
annamycin is not affected by p-glycoprotein, unlike doxorubicin and idarubicin
(Blood 88:633, 1996). Annamycin, whose fundamental mechanism of action appears
to be the inhibition of topoisomerase-II, was infused at a starting dose of 190
mg/m/day x 3 days with escalation to 230, 280, and 350 mg/m/day
x 3 days. Annamycin was generally well tolerated with no observed
cardiotoxicity. The MTD was determined at 280 mg/m/day x 3 days
with grade 3/4 hepatotoxicity and mucositis observed at the higher dose level.
Of the 21 patients registered, 1 was enrolled but not treated, two suffered
early deaths, sixteen failed to achieve CR, and 2 achieved CR (1 AML at 280
mg/m/day who had failed induction therapy with CAT, and 1 ALL at
350 mg/m/day who relapsed after allogeneic BMT). Fifty percent of all
patients cleared their circulating blasts and 43% their bone marrow blasts.
MDR-1 and MRP levels were determined before, during and after treatment and
were found not to prevent marrow aplasia. Conclusion: Annamycin is safe, well
tolerated and shows clinical activity in patients with acute leukemias. Further
evaluation of this novel anthracycline in patients with hematopoietic
malignancies is warranted.
Complete Remission (HCR) and Molecular Response Induced by Liposomal All-Trans-Retinoic
Acid (ATRA) in Acute Promyelocytic Leukemia (APL).
S. Santillana; Marion Faldas; Anthony H. Williams; Dan Douer; Kristi A.
Boehm (Profiled Author: Dan Douer) Blood 2001;96(11 PART II):217b.
Intravenous Liposomal All-Trans-Retinoic Acid (LipoATRA) in Children with Acute
Promyelocytic Leukemia (APL).
Wachtel, C. Pérez, J. Marcial, J. León, A. Williams, Marion Faldas, S. Santillana. Aronex Pharmaceuticals, The Woodlands, Texas,
USA; Instituto de Enfermedades Neoplasicas, Lima, Peru. Proc Int Soc Pedtr Oncol 2001 Abstract P333
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