Patt Y Z, Yoffe B, Charnsangavej C, Pazdur R, Fischer H, Cleary K, Roh M, Smith R, Noonan C A, Levin B
Department of Gastrointestinal Medical Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer. 1993 Nov 1;72(9):2574-82. doi: 10.1002/1097-0142(19931101)72:9<2574::aid-cncr2820720911>3.0.co;2-l.
A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment.
Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments.
Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen.
The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.
进行了一项II期临床试验，以评估静脉注射氟尿嘧啶（5-FU）和皮下注射重组干扰素-α-2b（rIFN-α-2b）治疗肝细胞癌（HCC）的疗效，并确定可能预测治疗反应的因素。
29例患者登记入组该方案。5-FU以持续静脉输注（剂量=750mg/m²）的方式连续给药5天。rIFN-α-2b在5-FU输注的第1、3和5天皮下注射（剂量=5×10⁶U/m²），每天1次。治疗每14天重复一次。在一个疗程治疗结束时评估反应，一个疗程相当于4次治疗。
在28例可评估反应的患者中，5例（18%）有部分反应，1例（4%）有轻微反应。反应持续时间超过2个月至超过24个月（中位数为11.5个月）。10例（36%）患者无反应，12例（43%）有疾病进展。6例有反应的患者属于血清甲胎蛋白（AFP）预处理水平为50ng/ml或更低的16例患者组，以及肿瘤累及肝实质50%或更少的8例患者组。54%的患者发生了粘膜炎，这是与治疗方案相关的最常见毒性反应。分别有16%和17%的患者观察到腹泻和皮炎；疲劳、血小板减少、粒细胞减少、神经毒性以及恶心和呕吐并不常见。
静脉注射5-FU和皮下注射rIFN-α-2b的方案耐受性良好，在血清AFP水平低且肝替代率为50%或更低的HCC患者中，有31%（16例中的5例）产生了持久的部分反应。相比之下，该治疗方案对血清AFP水平高或肝病广泛的HCC患者无效。
