Combined Treatment With Arsenic Trioxide and All-Trans-Retinoic Acid in Patients With Relapsed Acute Promyelocytic Leukemia

Author:

Raffoux Emmanuel1,Rousselot Philippe1,Poupon Joël1,Daniel Marie-Thérèse1,Cassinat Bruno1,Delarue Richard1,Taksin Anne-Laure1,Réa Delphine1,Buzyn Agnès1,Tibi Annick1,Lebbé Geneviève1,Cimerman Patricia1,Chomienne Christine1,Fermand Jean-Paul1,de Thé Hugues1,Degos Laurent1,Hermine Olivier1,Dombret Hervé1

Affiliation:

1. From the Department and Institut of Hematology, Hôpital Saint-Louis; Department of Biochemistry-Toxicology, Hôpital Fernand Widal; Department of Hematology, Hôpital Necker; Etablissement Pharmaceutique des Hôpitaux de Paris; and Délégation à la Recherche Clinique, Paris, France.

Abstract

Purpose: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. Patients and Methods: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. Results: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. Conclusion: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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