[Effects of combination therapy with all-trans retinoic acid and arsenic trioxide on acute promyelocytic leukemia].
OBJECTIVE
The mechanism of effect of arsenic trioxide on promyelocytic leukemia is different from that of all-trans retinoic acid. Arsenic trioxide exerts its action by accelerating cell apoptosis, while all-trans retinoic acid by inducing cell differentiation. However, both drugs can inhibit the transcription of tissue factor (TF) mRNA in acute promyelocytic leukemia, and decrease TF level and coagulative activity to normalize coagulopathy. The objective of the study was to observe whether combination of the two drugs could improve efficacy or in contrary accentuate adverse reactions.


METHODS
Two groups of patients with acute promyelocytic leukemia were included. Twenty-two patients (17 untreated cases and 5 relapsed cases) from January 2000 to October 2001 in group I were treated only with oral retinoic acid [25 mg/(m(2)x d) in two divided doses] for less than 50 days. Nineteen cases (15 untreated cases and 4 relapsed cases) from November 2001 to June 2003) in Group II were treated with combination of arsenic trioxide and all-trans retinoic acid. 0.1% AS2O3 10 ml in 500 ml 5% glucose solution was given intravenously for 4 to 6 hours per day for 28 days. The dosage of retinoic acid in group II was the same as that in group I.


RESULTS
Nineteen of 22 cases in retinoic acid-treated group (group I)(16 untreated cases and 3 relapsed cases) achieved complete remission (CR). The CR rate was 86.4%. Seventeen of 19 cases in combination therapy group (group II)(15 untreated cases and 2 relapsed cases) achieved CR. The CR rate was 89.5%. The death rates were 13.6% (3/22, 1 untreated case, 2 relapsed cases) in group I and 10.5% (2/19, 2 relapsed cases) in group II, respectively. The median time to CR was 23 days in group I and 26 days in group II, and the median time to normalization of coagulopathy was 7 days in group I and 4 days in group II. Significant differences were found between the two groups. No significant adverse reaction was observed in both groups.


CONCLUSIONS
The CR rate and death rate were not different between the two groups. The combination therapy with AS2O3 and all-trans retinoic acid can shorten the time to CR and normalization of coagulopathy.
Zhang
Guo-Cai
GC
Department of Hematology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, PR China. zhangguocai1946@21cn.com
Zheng
Dong
D
Li
Qun-Hua
QH
Luo
Shao-Kai
SK
Li
Juan
J
Peng
Ai-Hua
AH
Tong
Xiu-Zhen
XZ
Tan
En-Xun
EX
Hong
Wen-De
WD
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage*; D014212:Tretinoin / Q000008:administration & dosage*
D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide