Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Raffoux
Emmanuel
E
Department and Institute of Hematology, Hôpital Saint-Louis, Paris, France.
Rousselot
Philippe
P
Poupon
Jöel
J
Daniel
Marie-Thérèse
MT
Cassinat
Bruno
B
Delarue
Richard
R
Taksin
Anne-Laure
AL
Réa
Delphine
D
Buzyn
Agnès
A
Tibi
Annick
A
Lebbé
Geneviève
G
Cimerman
Patricia
P
Chomienne
Christine
C
Fermand
Jean-Paul
JP
de Thé
Hugues
H
Degos
Laurent
L
Hermine
Olivier
O
Dombret
Hervé
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage; D012008:Recurrence; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide