Combination therapy for head and neck cancer with CTL induced in vitro and low dose of anticancer drugs followed by iradiation.

对22例上颌窦癌患者进行了2个周期的小剂量化疗和过继免疫治疗。采集外周血单个核细胞(PBMC)后第4天或第5天，将插管逆行插入肿瘤供血动脉。次日分别动脉注射顺铂20 mg/只，卡铂100 mg/只，5-氟尿嘧啶250 mg/只，连续5天。在小剂量化疗中，用同种异体骨髓间充质干细胞和白介素2从自体PBMC中诱导细胞毒性T淋巴细胞(CTL)。在完成低剂量化疗后，这些体外诱导的CTL被动脉内回输给患者，并通过CT扫描评估其效果。随后，所有患者在对三种联合治疗进行评价的基础上，接受40Gy放疗，然后进行手术治疗。在22例患者中，1例完全缓解(CR)，14例部分缓解(PR)。共有13名患者(55%)在三种联合治疗后表现出临床完全缓解。在这13名临床CR患者中，11名在组织学上证实没有肿瘤残留，并且需要手术，没有可怜的功能和形态上的牺牲。两名组织学PR患者尽管术后再接受放射治疗，但仍出现复发。9例临床PR患者中，1例行眶内容物摘除等手术，3例行上颌骨切除(保留眶内容物)，5例行Denker手术(保留眶内容物和腭部)，7例复发。Kaplan-Meier生存率显示这些患者的5年生存率约为60%。这三种联合疗法给大约一半的MSC患者带来了疗效和良好的生活质量。

We applied 2 cycles of combination therapy with low dose chemotherapy and adoptive immunotherapy for 22 patients with maxillary sinus carcinoma (MSC). On 4th or 5th day after collection of peripheral blood mononuclear cells (PBMC), cannula were inserted retrogradely into tumor feeding artery. On the following day, cisplatin or carboplatin was injected intraarterially at 20 mg/body, 100 mg/body, respectively and 250 mg/body of 5-fluorouracil were administered on the subsequent 5 consecutive days. During the low dose chemotherapy, cytotoxic T lymphocyte (CTL) were induced from autologous PBMC using allogeneic MSC cell line and interleukin-2. After the completion of low dose chemotherapy, these in vitro-induced CTL were infused back intra-arterially to the patient, and the effects were estimated by CT scans. Subsequently, all the patients received 40 Gy-radiotherapy and then surgery on the basis of the evaluation on the three combination therapy. Of 22 patients, one and fourteen showed complete response (CR) and partial response (PR), respectively, to the chemo-immunotherapy. A total of 13 patients (55%) showed clinical CR in response to the three combined therapy. No residual tumor was confirmed histollogically in eleven of these thirteen clinical CR patients and required surgery without pitiful functional and morphological sacrifices. The two histlological PR patients occurred recurrence despite additional post-operative irradiation. In 9 clinical PR patients, surgery including orbital exenteration was carried out for one patients and the other 3 and 5 patients received maxillectomy (preserved orbital content) and Denker's operation (preserved both orbital content and palate), respectively and 7 occurred recurrence. Kaplan-Meier survival rate showed that 5 year survival rate of these patients were approximately 60%. The three combination therapy brought curative effect and good quality of life to approximately half of MSC patients.