Scadden D T, Bering H A, Levine J D, Bresnahan J, Evans L, Epstein C, Groopman J E
Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Clin Oncol. 1991;14 Suppl 1:S40-4. doi: 10.1097/00000421-199112001-00008.
Combined zidovudine (ZDV) and interferon-alpha (IFN) is an appealing therapy for AIDS-associated Kaposi's sarcoma because of the antiretroviral as well as antitumor potential of this combination. Overlapping myelotoxicity of these agents, however, frequently complicates their clinical use. This phase I/II study was undertaken to test the safety and efficacy of granulocyte-macrophage colony stimulating factor (GM-CSF) in those patients who became neutropenic while receiving ZDV (1,200 mg/day) and IFN (9 MU/day). Despite a "high-risk" population of patients, the tumor response rate among evaluable patients was 50% (33% overall). Sixty-four percent of patients required GM-CSF and all patients receiving GM-CSF had a prompt improvement in their absolute neutrophil count (ANC). The use of GM-CSF was associated with an improved end of study ANC (p less than 0.05), but was not associated with tumor response, CD4 count improvement, or improved change in hemoglobin concentration. GM-CSF/ZDV/IFN was not associated with increased toxicity over ZDV/IFN; however, two unusual events occurred in the GM-CSF/ZDV/IFN group: erythema multiforme and glucose intolerance. Dose-limiting thrombocytopenia and anemia were seen in two patients and anemia in one patient on GM-CSF/ZDV/IFN. No consistent alterations in serum HIV p24 antigenemia were noted in either group. The use of GM-CSF mitigated the neutropenia of combined ZDV and IFN. Further study evaluating the utility of this hematopoietic growth factor in combination therapies for AIDS patients is warranted.
齐多夫定（ZDV）与α干扰素（IFN）联合使用是治疗艾滋病相关卡波西肉瘤的一种有吸引力的疗法，因为这种联合用药具有抗逆转录病毒以及抗肿瘤的潜力。然而，这些药物重叠的骨髓毒性常常使它们的临床应用变得复杂。这项I/II期研究旨在测试粒细胞巨噬细胞集落刺激因子（GM-CSF）对那些在接受ZDV（1200毫克/天）和IFN（9百万单位/天）治疗时出现中性粒细胞减少的患者的安全性和疗效。尽管患者群体具有“高风险”，但可评估患者中的肿瘤缓解率为50%（总体为33%）。64%的患者需要GM-CSF，所有接受GM-CSF治疗的患者的绝对中性粒细胞计数（ANC）都迅速改善。GM-CSF的使用与研究结束时ANC的改善相关（p小于0.05），但与肿瘤缓解、CD4计数改善或血红蛋白浓度变化的改善无关。GM-CSF/ZDV/IFN与ZDV/IFN相比，毒性并未增加；然而，GM-CSF/ZDV/IFN组发生了两起不寻常事件：多形红斑和葡萄糖不耐受。在GM-CSF/ZDV/IFN组中，两名患者出现了剂量限制性血小板减少和贫血，一名患者出现了贫血。两组均未观察到血清HIV p24抗原血症的一致变化。GM-CSF的使用减轻了ZDV和IFN联合使用时的中性粒细胞减少。有必要进一步研究评估这种造血生长因子在艾滋病患者联合治疗中的效用。
