Stoter G, Shiloni E, Aamdal S, Cleton F J, Iacobelli S, Bijman J T, Palmer P, Franks C R, Rodenhuis S
Rotterdam Cancer Institute, The Netherlands.
Eur J Cancer Clin Oncol. 1989;25 Suppl 3:S41-3.
Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.
24例可评估的转移性黑色素瘤患者进入了一项多中心II期研究，接受两个周期的人重组白细胞介素-2（rIL-2）诱导治疗，剂量为18×10⁶IU/m²/天，在第1 - 5天和第12 - 17天持续静脉推注。第26天给予达卡巴嗪（DTIC）850mg/m²静脉推注。每五周重复一个周期。诱导治疗完成三周后安排维持治疗，包括rIL-2 18×10⁶IU/m²/天，持续五天，与DTIC 850mg/m²静脉注射交替进行，每三周一次，共18周。中位年龄为44岁（范围23 - 80岁），卡诺夫斯基指数为100（范围80 - 100）。1例患者曾接受羟基脲化疗，1例患者曾接受放疗。6例患者有反应（25%）：2例完全缓解（CR），4例部分缓解（PR）。5例患者病情稳定（SD）。反应发生在以下部位：肝脏2/9（22%），肺3/14（21%），皮肤2/11（18%），淋巴结3/12（25%）。CR持续时间分别为11 +和13个月。PR持续时间分别为2、5、7和11 +个月。值得注意的是，SD患者的疾病进展时间与有反应者相似：4、4、11 +、11 +和14 +个月。毒性反应包括大多数患者出现发热、皮疹、疲劳、厌食和腹泻。2例患者体重增加超过10%。4例患者出现需要血管活性药物或中断rIL-2治疗的低血压，7例患者肌酐升高至WHO 1 - 2级，6例患者胆红素升高至WHO 1 - 3级。1例患者出现短暂性室性心动过速。看来按此方案使用rIL-2和DTIC是可行且有效的，但并不明显优于单独使用rIL-2。
