Mavligit G M, Zukiwski A A, Charnsangavej C, Carrasco C H, Wallace S, Gutterman J U
Department of Clinical Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer. 1992 Jan 15;69(2):557-61. doi: 10.1002/1097-0142(19920115)69:2<557::aid-cncr2820690246>3.0.co;2-q.
Twenty-two chemotherapy-resistant patients with liver metastases received 46 courses of recombinant human tumor necrosis factor (rhTNF) administered by 5-day continuous infusion through percutaneously inserted hepatic arterial catheters. The maximum tolerated daily dose of rhTNF was 150 micrograms/m2. This is six times the maximum tolerated daily dose of rhTNF that could be given systemically (intravenous) on the same schedule. The dose-limiting toxicity resulted in severe, although transient, hypophosphatemia (less than 1.0 mg/dl) associated with myocardial dysfunction. Objective tumor response (partial tumor response or greater) was observed in 2 of 14 patients (14%) with colorectal cancer and lasted as long as 3 months. Three additional minor responses occurred among these patients with colorectal cancer. Plasma carcinoembryonic antigen levels also decreased significantly (greater than 25%) in 7 of the 14 (50%) patients with colorectal cancer. Regional biologic therapy with rhTNF as a sole modality has definite antitumor activity in colorectal cancer metastatic to the liver and warrants additional study in previously untreated patients.
22例化疗耐药的肝转移患者通过经皮插入肝动脉导管进行5天持续输注，接受了46个疗程的重组人肿瘤坏死因子（rhTNF）治疗。rhTNF的最大耐受日剂量为150微克/平方米。这是按照相同给药方案全身（静脉）给药时rhTNF最大耐受日剂量的6倍。剂量限制性毒性导致严重但短暂的低磷血症（低于1.0毫克/分升）并伴有心肌功能障碍。在14例结直肠癌患者中有2例（14%）观察到客观肿瘤反应（部分肿瘤反应或更好），持续长达3个月。这些结直肠癌患者中另外还有3例出现轻微反应。在14例（50%）结直肠癌患者中，有7例患者的血浆癌胚抗原水平也显著下降（超过25%）。以rhTNF作为单一治疗手段的区域生物治疗对转移至肝脏的结直肠癌具有明确的抗肿瘤活性，值得在未接受过治疗的患者中进一步研究。
