Tomita Y, Katagiri A, Saito K, Imai T, Saito T, Tanikawa T, Terunuma M, Nishiyama T, Takahashi K
Department of Urology, Niigata University School of Medicine, Japan.
Int J Urol. 1998 Jan;5(1):16-21. doi: 10.1111/j.1442-2042.1998.tb00227.x.
Initial results of adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) appeared to offer promise for treating renal cell cancer (RCC). However, lower response rates were seen in subsequent trials, and the long-term results of this treatment method have not been fully reported. In this study, we examine long-term results of adoptive immunotherapy using LAK cells, IL-2, and cyclophosphamide (LAK/IL-2/CPM therapy).
We administered 10 courses of therapy to 9 patients with advanced RCC. One patient had liver and para-aortic lymph node metastases; the others had only lung metastases. The clinical effects were initially evaluated 4 weeks after therapy and follow-up was continued for periods of 43 to 76 months.
The 4-week evaluation revealed 3 complete responses (CR), 3 partial responses (PR), 1 minor response (MR), 1 patient with no change in disease status (NC), and 2 patients whose disease progressed (PD). One CR patient remained apparently free of disease for 43 months. After tumors recurred in the lung of another CR patient further disease progression was suppressed by IL-2 administration until the patient died from other causes at 46 months. The third CR patient showed tumor recurrence in the lung and was re-treated with the same LAK/CPM/IL-2 therapy. Lung tumors decreased in size (PR), but the patient died due to brain metastasis 2 months after the second round of treatment. The 2 initial PR patients, as well as the MR and NC patients, developed regrowth or new metastatic lesions within 2 to 15 months following therapy. The 2 PD patients died 2 and 9 months after therapy.
Long-term effects of LAK/IL-2/CPM therapy were not correlated with the maximal response observed 4 weeks after therapy. Although LAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our data suggest that long-term suppression will require surgical removal of remnant tumors or more intensive maintenance therapy.
使用淋巴因子激活的杀伤细胞（LAK）和白细胞介素-2（IL-2）进行过继性免疫治疗的初步结果似乎为治疗肾细胞癌（RCC）带来了希望。然而，在随后的试验中观察到较低的缓解率，且这种治疗方法的长期结果尚未得到充分报道。在本研究中，我们考察了使用LAK细胞、IL-2和环磷酰胺（LAK/IL-2/CPM疗法）进行过继性免疫治疗的长期结果。
我们对9例晚期RCC患者给予10个疗程的治疗。1例患者有肝脏和主动脉旁淋巴结转移；其他患者仅有肺转移。治疗后4周初步评估临床疗效，并持续随访43至76个月。
4周评估显示3例完全缓解（CR）、3例部分缓解（PR）、1例轻度缓解（MR）、1例疾病状态无变化（NC）患者以及2例疾病进展（PD）患者。1例CR患者在43个月内明显无疾病复发。另1例CR患者肺部肿瘤复发后，通过给予IL-2抑制了疾病的进一步进展，直至该患者在46个月时死于其他原因。第3例CR患者肺部出现肿瘤复发，并接受相同的LAK/CPM/IL-2疗法再次治疗。肺部肿瘤缩小（PR），但患者在第二轮治疗后2个月因脑转移死亡。2例初始PR患者以及MR和NC患者在治疗后2至15个月内出现肿瘤复发或新的转移病灶。2例PD患者在治疗后2个月和9个月死亡。
LAK/IL-2/CPM疗法的长期疗效与治疗后4周观察到的最大缓解不相关。虽然LAK/IL-2/CPM疗法似乎适合用作RCC的诱导治疗，但我们的数据表明，长期抑制需要手术切除残余肿瘤或更强化的维持治疗。
