Effect of intravenous infusions of 12-O-tetradecanoylphorbol-13-acetate (TPA) in patients with myelocytic leukemia: preliminary studies on therapeutic efficacy and toxicity.
Studies by several investigators have shown that 12-0-tetradecanoylphorbol-13-acetate (TPA) is an extraordinarily potent stimulator of differentiation of cultured human promyelocytic leukemia cells in vitro. In the present study, TPA was administered to humans by i.v. infusion without irreversible toxicity, and it was shown to have pharmacological activity for the treatment of myelocytic leukemia in patients refractory to cytosine arabinoside (Ara C), retinoic acid, and other antileukemic drugs. Marked decreases in bone marrow myeloblasts as well as temporary remission of disease symptoms were observed when TPA was administered alone or in combination with vitamin D3 and Ara C. Additional studies with TPA after the determination of optimum dosing regimens are needed to determine whether long-lasting or permanent remissions of myelocytic leukemia can be achieved. Transient and reversible side effects were observed after a 1-mg i.v. dose of TPA, but these adverse effects became less intense or disappeared when a lower dose of TPA was used. The results of this study indicate a therapeutic effect of TPA in patients with myelocytic leukemia.
Han
Z T
ZT
Henan Tumor Research Institute, Zheng Zhou, Henan 450000, People's Republic of China.
Zhu
X X
XX
Yang
R Y
RY
Sun
J Z
JZ
Tian
G F
GF
Liu
X J
XJ
Cao
G S
GS
Newmark
H L
HL
Conney
A H
AH
Chang
R L
RL
D000328:Adult; D000368:Aged; D002762:Cholecalciferol / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects / Q000627:therapeutic use*
D003561:Cytarabine; D002762:Cholecalciferol; D013755:Tetradecanoylphorbol Acetate