LoRusso P M, Aukerman S L, Polin L, Redman B G, Valdivieso M, Biernat L, Corbett T H
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48202-0188.
Cancer Res. 1990 Sep 15;50(18):5876-82.
Recombinant interleukin-2 (IL-2)/chemotherapy combinations have recently entered clinical trial. The rationale for sequencing has primarily been empiric or based on in vitro data. To establish in vivo models for chemoimmunotherapy trials, we investigated IL-2 alone and in combination with dacarbazine (DTIC) and adriamycin. IL-2 (as a single agent given i.v. at 1-3 x 10(5) Cetus units once daily for 5 days, repeated 7-10 days later), was highly active against an immunogenic line of colon adenocarcinoma no. 11/A [tumor growth inhibition (T/C) = 0% with cures]. It was modestly active against colon adenocarcinoma no. 38 (T/C = 39%), mammary adenocarcinoma no. 16/C (T/C = 18%), and B16 melanoma (T/C = 21%). IL-2 was inactive against colon adenocarcinoma no. 7/A (T/C = 83%). Combination trials were done using DTIC and IL-2 against colon no. 7/A and upstaged colon no. 11/A. The combination of adriamycin and IL-2 was tested against mammary adenocarcinoma no. 16/C. In the DTIC/IL-2 combination trials, the combination was superior over either agent used alone. In the IL-2/adriamycin trials, the combination was no better than adriamycin alone at optimum dosages.
重组白细胞介素-2(IL-2)/化疗联合方案最近已进入临床试验阶段。联合治疗顺序的选择依据主要是经验性的或基于体外实验数据。为建立化学免疫治疗试验的体内模型,我们研究了单独使用IL-2以及将其与达卡巴嗪(DTIC)和阿霉素联合使用的情况。IL-2(作为单一药物,静脉注射,剂量为1 - 3×10⁵ 赛特斯单位,每日一次,共5天,7 - 10天后重复给药)对免疫原性结肠癌11/A号株具有高度活性[肿瘤生长抑制率(T/C)= 0%,有治愈病例]。对结肠癌38号株(T/C = 39%)、乳腺腺癌16/C号株(T/C = 18%)和B16黑色素瘤(T/C = 21%)有中等活性。IL-2对结肠癌7/A号株无活性(T/C = 83%)。使用DTIC和IL-2联合对结肠癌7/A号株和进展期结肠癌11/A号株进行了联合试验。使用阿霉素和IL-2联合对乳腺腺癌16/C号株进行了试验。在DTIC/IL-2联合试验中,联合用药优于单独使用任何一种药物。在IL-2/阿霉素试验中,在最佳剂量下联合用药并不比单独使用阿霉素效果更好。