Dusenbery K E, McGuire W A, Holt P J, Carson L F, Fowler J M, Twiggs L B, Potish R A
University of Minnesota Hospital and Clinic, Department of Radiation Oncology 55455.
Int J Radiat Oncol Biol Phys. 1994 Jul 30;29(5):1079-84. doi: 10.1016/0360-3016(94)90403-0.
Anemia during radiation therapy independently predicts poor outcome in patients with cervical cancer. Despite a randomized trial demonstrating red cell transfusions improve local control and survival, many patients are not transfused due to toxicity concerns. This study evaluates the efficacy of recombinant human erythropoietin (r-HuEPO) in reversing anemia in patients undergoing radiation therapy.
Twenty patients with criteria of anemia (Hgb < 12.5 g/dL) and surgically staged cervical cancer FIGO stages IB (n = 7), IIA (n = 1), IIB (n = 9), and IIIB (n = 3), ranging in ages from 23-75 years (median 43), were included in this Phase I/II study. Fifteen were treated with r-HuEPO (200 U/kg/day) and ferrous sulfate 5-10 days prior to initiation of external beam radiation therapy, continuing until Hgb was < or = 14 g/dL or completion of radiation therapy. Five patients were treated with ferrous sulfate alone. An additional 61 historical controls meeting eligibility criteria were analyzed. All received external beam radiation therapy and two intracavitary cesium applications. Cisplatinum chemotherapy (20 mg/m2/week) was given as a radiosensitizer in 14 r-HuEPO patients, 4 concurrent controls, and 17 historical controls.
A marked reticulocytosis was seen in the r-HuEPO group, but not the study controls. In the r-HuEPO group, the mean +/- SD serum Hgb rose + 30% over the course of radiation therapy from a baseline of 10.3 +/- 1.04 g/dL to 13.2 +/- 1.7 g/dL. Average increase in Hgb was 0.5 g/dL per week. Average Hgb during RT was 13.4 g/dL. In study and historical controls, mean initial Hgb levels were 10.7 +/- 1.04 g/dL and 11.1 +/- 1.3g/dL, respectively, remaining unchanged over the course of radiation therapy. Average Hgb levels during radiation therapy were 11.1 g/dL in study controls and 11.4 g/dL in historical controls, significantly lower than r-HuEPO patients (p = 0.0001). Erythropoietin was well tolerated. There were no significant differences in white blood counts (p = 0.6) or platelet counts (p = 0.4) between r-HuEPO patients and both control groups. No patients had blood pressure changes during r-HuEPO therapy. The only possible side effect was deep venous thrombosis, occurring in two patients who were withdrawn from r-HuEPO therapy. Two additional patients developed deep venous thrombosis 9 and 10 days after radiation therapy and r-HuEPO were completed.
Erythropoietin appears to be both safe and effective at raising Hgb levels in anemic cervical cancer patients receiving radiation therapy and chemotherapy.
放射治疗期间的贫血独立预示着宫颈癌患者的不良预后。尽管一项随机试验表明红细胞输血可改善局部控制和生存率，但由于对毒性的担忧，许多患者未接受输血治疗。本研究评估重组人促红细胞生成素（r-HuEPO）在逆转接受放射治疗患者贫血方面的疗效。
本I/II期研究纳入了20例符合贫血标准（血红蛋白<12.5 g/dL）且经手术分期的宫颈癌患者，国际妇产科联盟（FIGO）分期为IB期（n = 7）、IIA期（n = 1）、IIB期（n = 9）和IIIB期（n = 3），年龄在23 - 75岁之间（中位数43岁）。15例患者在开始外照射放疗前5 - 10天接受r-HuEPO（200 U/kg/天）和硫酸亚铁治疗，持续至血红蛋白≤14 g/dL或放疗结束。5例患者仅接受硫酸亚铁治疗。另外分析了61例符合入选标准的历史对照患者。所有患者均接受外照射放疗和两次腔内铯照射。14例接受r-HuEPO治疗的患者、4例同期对照患者和17例历史对照患者接受顺铂化疗（20 mg/m²/周）作为放射增敏剂。
r-HuEPO组出现明显的网织红细胞增多，但研究对照组未出现。在r-HuEPO组，放射治疗期间血清血红蛋白平均值±标准差从基线的10.3±1.04 g/dL上升了30%，至13.2±1.7 g/dL。血红蛋白平均每周增加0.5 g/dL。放疗期间平均血红蛋白为13.4 g/dL。在研究对照组和历史对照组中，初始血红蛋白平均水平分别为10.7±1.04 g/dL和11.1±1.3 g/dL，在放射治疗过程中保持不变。研究对照组放疗期间平均血红蛋白水平为11.1 g/dL，历史对照组为11.4 g/dL，显著低于r-HuEPO治疗的患者（p = 0.0001）。促红细胞生成素耐受性良好。r-HuEPO治疗患者与两个对照组之间白细胞计数（p = 0.6）或血小板计数（p = 0.4）无显著差异。r-HuEPO治疗期间无患者出现血压变化。唯一可能的副作用是深静脉血栓形成，2例患者因出现此情况退出r-HuEPO治疗。另外2例患者在放疗和r-HuEPO治疗结束后9天和10天出现深静脉血栓形成。
促红细胞生成素在提高接受放疗和化疗的贫血宫颈癌患者血红蛋白水平方面似乎既安全又有效。
