Donovan P B, Kaplan M E, Goldberg J D, Tatarsky I, Najean Y, Silberstein E B, Knospe W H, Laszlo J, Mack K, Berk P D
Am J Hematol. 1984;17(4):329-34. doi: 10.1002/ajh.2830170402.
Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.
真性红细胞增多症（PV）采用放射性磷或烷化剂进行传统治疗会显著增加急性白血病、胃肠道癌和皮肤癌的发病风险。因此，治疗这种疾病需要一种无致突变性的药物。对118例患者给予羟基脲（HU），负荷剂量为30mg/kg/天，持续1周，之后减至15mg/kg/天。超过80%的患者在12周内实现了对升高的血细胞比容和血小板计数的初步控制。定义了长期疾病控制情况，既往未治疗患者的1年无失败生存率累计为73%，既往接受过其他骨髓抑制治疗的患者为59%。HU耐受性良好，血细胞减少症一般在治疗的前8周内出现，为一过性，临床意义不大。然而，鉴于这种毒性，建议初始给予HU的剂量为15 - 20mg/kg/天。3例患者发生了急性白血病；2例未接受过治疗，1例接受过骨髓抑制治疗。羟基脲是治疗PV的有效药物，但有必要持续评估其致突变潜力。
