Marcus S L, Petrylak D P, Dutcher J P, Paietta E, Ciobanu N, Strauman J, Wiernik P H, Hutner S H, Frank O, Baker H
Medical Research Division, Lederle Laboratories, Pearl River, NY 10965.
Am J Clin Nutr. 1991 Dec;54(6 Suppl):1292S-1297S. doi: 10.1093/ajcn/54.6.1292s.
Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10(5) units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m2 continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 +/- 14.2 mumol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 +/- 4.5 mumol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 mumol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (less than 2.8 mumol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.
15例转移性恶性黑色素瘤、肾癌和结肠癌患者接受了三阶段过继性免疫治疗方案:第1阶段,每8小时静脉注射10(5)单位(高剂量)白细胞介素-2(IL-2)或1mg/m2持续静脉输注;第2阶段,休息6.5天并进行白细胞分离术;第3阶段,4天高剂量IL-2加三次自体淋巴因子激活的杀伤细胞输注。治疗的毒性包括发热、寒战、心动过速、低血压、呕吐、腹泻和液体潴留。进入试验的患者没有营养不良,治疗前血浆维生素C平均浓度正常(36.3±14.2μmol/L)。仅用高剂量IL-2进行第一阶段治疗后,平均浓度下降了80%(降至7.4±4.5μmol/L)。在整个15天的治疗剩余时间里,血浆维生素C平均浓度仍严重缺乏(在4.5至7.4μmol/L之间)。在此期间,15例患者中有12例的维生素C浓度检测不到(低于2.8μmol/L)。在治疗的各个阶段,所有接受检测的患者血液泛酸和血浆维生素E浓度均保持在正常范围内。