Braun D P, Bonomi P D, Taylor S G, Harris J E
J Biol Response Mod. 1987 Jun;6(3):331-45.
We have attempted to modify the manner in which chemotherapy influences immune function in lung cancer patients by adding the nonsteroidal, antiinflammatory drug (NSAID) piroxicam to a cytotoxic drug treatment regimen. Eighteen previously untreated patients with lung cancer received cytotoxic chemotherapy with mitomycin-C (10 mg/m2), vinblastine (6 mg/m2), and cis-platinum (40 mg/m2) (MVP) on day 1 of a 21-day treatment cycle; 12/18 patients also received piroxicam (20 mg/day) beginning 10 days prior to MVP and persisting throughout the 21-day treatment cycle. In vitro tests included (a) phytohemagglutinin (PHA) responsiveness in the presence of indomethacin or interleukin-2 (IL-2), (b) natural killer cell (NK) function, and (c) PHA-induced IL-2 synthesis. In the 6 patients treated with MVP alone, depressed PHA reactivity was found pretherapy, which was augmented by indomethacin, but not by IL-2; this was associated with impaired production of IL-2. By days 7-14, PHA reactivity, IL-2 responsiveness, and IL-2 production rebounded to normal. By days 14-21, PHA reactivity had declined once again in association with increased indomethacin-regulation and impaired IL-2 responsiveness and production. In the 12 patients who received MVP plus piroxicam, PHA and IL-2 assays improved by days 7-14 and indomethacin-regulation was normal; moreover, this improvement persisted throughout the 21-day treatment cycle. Immunological rebound persisted through as many as 3 consecutive 21-day MVP plus piroxicam treatment cycles in patients who were continuously monitored. In contrast to these results, piroxicam did not alter the way chemotherapy affected NK function. These results demonstrate that the immunomodulatory effects of cytotoxic chemotherapy can be modified or ameliorated by adding an NSAID to the cytotoxic drug treatment regimen; for certain functions, such as mitogen-stimulated blastogenesis or IL-2 production, sustained immunological rebound without immunosuppression can be achieved by this maneuver.
我们试图通过在细胞毒性药物治疗方案中添加非甾体类抗炎药（NSAID）吡罗昔康，来改变化疗对肺癌患者免疫功能的影响方式。18例既往未接受过治疗的肺癌患者在21天治疗周期的第1天接受丝裂霉素-C（10mg/m²）、长春碱（6mg/m²）和顺铂（40mg/m²）（MVP）的细胞毒性化疗；18例患者中有12例在MVP治疗前10天开始服用吡罗昔康（20mg/天），并持续整个21天治疗周期。体外试验包括：（a）在吲哚美辛或白细胞介素-2（IL-2）存在的情况下植物血凝素（PHA）反应性；（b）自然杀伤细胞（NK）功能；（c）PHA诱导的IL-2合成。在仅接受MVP治疗的6例患者中，治疗前发现PHA反应性降低，吲哚美辛可增强PHA反应性，但IL-2不能；这与IL-2产生受损有关。到第7 - 14天，PHA反应性、IL-2反应性和IL-2产生恢复正常。到第14 - 21天，PHA反应性再次下降，同时吲哚美辛调节增加，IL-2反应性和产生受损。在接受MVP加吡罗昔康治疗的12例患者中，到第7 - 14天PHA和IL-2检测结果有所改善，吲哚美辛调节正常；此外，这种改善在整个21天治疗周期中持续存在。在持续监测的患者中，免疫反弹在多达3个连续的21天MVP加吡罗昔康治疗周期中持续存在。与这些结果相反，吡罗昔康并未改变化疗对NK功能的影响方式。这些结果表明，在细胞毒性药物治疗方案中添加NSAID可以改变或改善细胞毒性化疗的免疫调节作用；对于某些功能，如丝裂原刺激的母细胞形成或IL-2产生，通过这种方法可以实现持续的免疫反弹而无免疫抑制。
