A pilot study on safety and pharmacokinetics of infliximab for the cancer anorexia/weight loss syndrome in non-small-cell lung cancer patients
A pilot study on safety and pharmacokinetics of infliximab for the cancer anorexia/weight loss syndrome in non-small-cell lung cancer patients
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DOI：
10.1007/s00520-004-0638-x
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发表时间：
2004-12-01
影响因子：
3.1
通讯作者：
Loprinzi, CL
中科院分区：
文献类型：
--
作者：
Jatoi, A;Jett, JR;Loprinzi, CL
背景：体重减轻预示着非小细胞肺癌患者的预后不良。肿瘤坏死因子 α (TNFα) 是这种体重减轻的调节剂，但尚无研究测试英夫利昔单抗（一种 IgG 单克隆抗体，可阻断 TNFα 与其 p55 和 p75 受体结合）用于此适应症。这项初步研究探讨了英夫利昔单抗与多西他赛（一种常用的非小细胞肺癌化疗药物）联合使用的安全性和药代动力学。方法/结果：4 名转移性非小细胞肺癌患者最初接受英夫利昔单抗 5 mg/kg 静脉注射治疗，在第 1、3 和 5 周每周静脉注射一次，并在 8 周治疗周期的第 1、2、3、4、5 和 6 周每天静脉注射多西他赛 36 mg/m(2)。治疗耐受性良好，未出现 4 级或 5 级不良事件。第 1、3 和 5 周时英夫利昔单抗的最大血清浓度分别为（平均值 +/- SD）108 +/- 11、135 +/- 19 和 139 +/- 6 mug/ml，并且与未接受伴随化疗的非癌症患者的历史浓度（144 +/- 68 mug/ml）相似。一名患者表现出体重稳定。一名患者表现出部分肿瘤反应，一名患者表现出疾病稳定，两名患者表现出疾病进展。该队列的中位生存期为 203 天（范围 111 至 324 天）。结论：上述组合似乎是安全的，多西他赛似乎不会增加英夫利昔单抗的血清浓度。一项更大规模的研究正在进行中，测试该组合对非小细胞肺癌患者减肥的作用，并使用上述剂量。
Background: Weight loss predicts a poor prognosis for patients with non-small-cell lung cancer. Tumor necrosis factor alpha (TNFalpha) is a mediator of this weight loss, yet no studies have tested infliximab, an IgG monoclonal antibody that blocks the binding of TNFalpha to its p55 and p75 receptors, for this indication. The safety and pharmacokinetics of infliximab in combination with docetaxel, a commonly used chemotherapy agent for non-small-cell lung cancer, were explored in this pilot study. Methods/Results: Four patients with metastatic non-small-cell lung cancer were treated initially with infliximab 5 mg/kg per day intravenously once a week on weeks 1, 3 and 5, and docetaxel 36 mg/m(2) per day intravenously once a week on weeks 1, 2, 3, 4, 5 and 6 of an 8-week treatment cycle. Therapy was well tolerated with no grade 4 or 5 adverse events. Maximal serum concentrations of infliximab at 1, 3 and 5 weeks were (mean +/- SD) 108 +/- 11, 135 +/- 19, and 139 +/- 6 mug/ml, respectively, and appeared similar to historical concentrations from non-cancer patients not receiving concomitant chemotherapy (144 +/- 68 mug/ml). One patient manifested weight stability. One patient manifested a partial tumor response, one stable disease, and two disease progression. Median survival within the cohort was 203 days (range 111 to 324 days). Conclusions: The above combination appears safe, and docetaxel does not appear to increase serum concentrations of infliximab. A larger study testing the role of this combination for weight loss in non-small-cell lung cancer patients is ongoing and utilizes the doses described above.