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目的：观察国人对重组人肿瘤坏死因子衍生物 a（ recombined human tumor necrosis factorα derivative,rhTNFα Da）注射液的耐受程度，毒副反应的表现及与剂量的关系，确定人体安全耐受剂量。方法： rhTNFα Da的剂量分 6级，由初试剂量 (1× 106 IU/d)开始逐级增加，每剂量级 3～ 7例共 19例。 rhTNFα Da加入 0.9％ NaCl 100 ml中静脉点滴， 50 min内滴完。连续给药 5天，停药后再观察 2周。结果：病人的主要毒副作用为发热 (89.5％ )、寒战 (87.9％ )、头痛 (26.3％ )，部分病人有恶心、呕吐。 1例恶性黑色素瘤病人达到部分缓解，客观有效率为 12.5％。结论：发热、寒战为 rhTNFα Da的主要剂量限制性毒性。 rhTNFα Da的人体最大耐受剂量为 4× 106 IU／ d。推荐Ⅱ期临床研究剂量为 3× 106 IU／ d。初步观察发现对恶性黑色素瘤有一定的客观疗效，有效率为 12.5％。
OBJECTIVE: To observe the tolerability of recombinant human tumor necrosis factor-α (rhTNFα Da) injection, the performance of toxic side effects and the relationship with dose, and to determine the safe tolerated dose in humans. . Methods: The dose of rhTNFα Da was divided into six grades. The dose of rhTNFα Da was gradually increased from the initial dose (1×106 IU/d). There were 19 cases of 3 to 7 cases of each dose. The rhTNFα Da was added to 0.9% NaCl 100 ml intravenously and dripped within 50 min. Dosing was continued for 5 days, followed by observation for 2 weeks after discontinuation. Results: The main toxic side effects of patients were fever (89.5%), chills (87.9%), headache (26.3%), and some patients had nausea and vomiting. One patient with malignant melanoma achieved partial remission, with an objective and effective rate of 12.5%. Conclusion: Fever and chills are the main dose-limiting toxicities of rhTNFα Da. The human maximal tolerated dose of rhTNFα Da was 4 × 106 IU/day. The recommended phase II clinical study dose is 3 x 106 IU/day. Initial observations revealed a certain degree of objective efficacy for malignant melanoma, with an effective rate of 12.5%.