注射用重组改构人肿瘤坏死因子-NC(rhTNF-NC)治疗恶性肿瘤的Ⅱ期临床研究

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目的观察重组改构人肿瘤坏死因子-NC(rh TNF-NC)注射液单药治疗恶性肿瘤的临床疗效、不良反应以及对患者生活质量的影响。方法入组的320例患者中,可进行疗效评价310例,脱落9例,剔除1例。310例患者中,恶性淋巴瘤71例,恶性胸腹水169例,恶性黑色素瘤18例,肺癌20例,肝癌12例,乳腺癌10例,结肠癌7例和肾癌3例。恶性淋巴瘤、恶性黑色素瘤、肺癌等实体肿瘤患者给予静脉注射rh TNF-NC 60万~90万IU/m2,最大剂量≤100万IU/m2,1次/d,连用4周;恶性胸腹水患者予以胸腹腔注射rh TNF-NC,剂量为200万~300万IU/次,1~2次/周,连用2~3周;体表肿瘤(主要为恶性黑色素瘤)患者在rh TNF-NC静脉给药的同时予以瘤体内或瘤床注射,推荐注射剂量为50万~100万IU/次,2~3次/周。结果可评价的患者310例,其中恶性胸腹水169例,实体肿瘤141例。实体瘤患者中获CR 2例,PR 21例,有效率(RR)为16.3%(23/141),疾病控制率(DCR)为79.4%(112/141)。恶性淋巴瘤的RR为28.2%(20/71),DCR为84.5%(60/71);恶性黑色素瘤的RR为11.1%(2/18),DCR为83.3%(15/18);肺癌无CR病例,获PR 1例,MR 2例;肾癌获MR 1例;肝癌、结肠癌、乳腺癌均未见明显疗效。恶性胸腹水病例中获CR 15例,PR 102例,RR为69.2%(117/169),DCR为98.8%(167/169);其中,恶性胸水的RR为74.5%(105/141),恶性腹水为42.9%(12/28)。全组患者治疗后的KPS评分较治疗前有显著提高(P=0.013),特别是恶性胸水患者提高更为明显。主要不良反应为发热(38.8%)和寒战(23.5%),绝大多数为1、2级。结论注射用rh TNF-NC治疗恶性淋巴瘤和恶性胸腹水疗效明确,对肺癌、恶性黑色素瘤也有一定疗效,并能够明显改善各种癌症患者的生活质量,安全性良好。 Objective To observe the clinical efficacy, side effects and adverse effects on the quality of life of patients with recombinant tumor necrosis factor-NC (rh TNF-NC) single-agent in the treatment of malignant tumors. Methods Among the 320 patients enrolled, 310 cases could be evaluated, 9 cases dropped off, and 1 case was excluded. Of the 310 patients, 71 were malignant lymphomas, 169 were malignant ascites, 18 were malignant melanoma, 20 were lung cancer, 12 were liver cancer, 10 were breast cancer, 7 were colon cancer, and 3 were renal cancer. Malignant lymphoma, malignant melanoma, lung cancer and other solid tumor patients given intravenous rh TNF-NC 600,000 ~ 900,000 IU / m2, the maximum dose ≤ 1,000,000 IU / m2, 1 / d, for 4 weeks; malignant pleural effusion Patients were given intraperitoneal injection of rh TNF-NC, the dose of 2 million to 3 million IU / time, 1 or 2 times / week, once every 2 to 3 weeks; body surface tumors (mainly malignant melanoma) patients in rh TNF-NC Intravenous injection to the tumor or tumor bed injection, the recommended injection dose of 500,000 to 1 million IU / time, 2 to 3 times / week. Results A total of 310 evaluable patients were diagnosed, including 169 malignant pleural effusion and 141 solid tumors. Among the solid tumors, 2 were CR and 21 were PR. The effective rate (RR) was 16.3% (23/141) and the disease control rate (DCR) was 79.4% (112/141). The RR of malignant lymphoma was 28.2% (20/71) and the DCR was 84.5% (60/71). The malignant melanoma had RR of 11.1% (2/18) and DCR of 83.3% (15/18) CR cases, PR 1 cases, MR 2 cases; kidney cancer was MR 1 cases; no significant effect of liver cancer, colon cancer, breast cancer. Malignant pleural effusion in the case of CR 15 cases, PR 102 cases, RR was 69.2% (117/169), DCR was 98.8% (167/169); of which malignant pleural effusion RR was 74.5% (105/141), malignant Ascites was 42.9% (12/28). The KPS scores of all the patients after treatment were significantly higher than those before treatment (P = 0.013), especially in patients with malignant pleural effusion. The main adverse reactions were fever (38.8%) and chills (23.5%), the vast majority of 1,2. Conclusion rh TNF-NC for the treatment of malignant lymphoma and malignant pleural effusion clear effect on lung cancer, malignant melanoma have a certain effect, and can significantly improve the quality of life of various cancer patients, good safety.
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