Shiloni E, Pouillart P, Janssens J, Splinter T, Di Peri T, Symann M, Roest G J, Palmer P A, Franks C R
Hadassah University Hospital, Jerusalem, Israel.
Eur J Cancer Clin Oncol. 1989;25 Suppl 3:S45-9.
Between April 1988 and August 1989, 30 melanoma patients were entered in a multicentre Phase II study of dacarbazine (DTIC) 850 mg/m2 i.v. bolus on day 1, and recombinant interleukin-2 (rIL-2) (Cetus) 18 x 10(6) IU/m2/day i.v. continuous infusion on days 4-9. Six treatment cycles were given: the first two at an interval of 13 days, and further cycles at intervals of 20 days. Twenty patients are currently evaluable for toxicity and 18 for response. Two of these patients presented with metastatic intraocular melanoma. Median age was 48 years (range 18-83), and median Karnofsky index was 100 (range 80-100). Four patients had received prior radiotherapy and one had received prior immunotherapy. Seventeen patients received two cycles of treatment and nine patients received three or more cycles. Four patients responded (22%): two complete remissions and two partial remissions. Stable disease was seen in six patients (33%). Responses occurred in the lung, skin, spleen and lymph nodes. Seventy-five percent of the patients received the full dose of rIL-2 during cycle 1, whilst only 2 out of 9 (22%) received the planned dose on the third cycle. Rebound lymphocytosis of 5.3 x 10(3)/L (range 1.2-18.1) occurred 24-48 h after rIL-2, but was not predictive for response. Currently, there is no evidence that pretreatment with DTIC impacts negatively on the rIL-2-stimulated lymphocyte proliferation. The toxicity profile of this treatment regimen did not differ significantly from that already described for similar regimens of rIL-2. However, in this interim analysis, there was a trend for a higher percentage of patients (25%) to experience severe weight gain (greater than 10%). This study shows that this treatment regimen is active in metastatic melanoma, with acceptable toxicity. Further research will focus on using other chemotherapeutic agents and/or other biological response modifiers (e.g. interferons, tumour necrosis factor) in combination with rIL-2.
1988年4月至1989年8月期间，30例黑色素瘤患者进入一项多中心II期研究，接受如下治疗：第1天静脉推注达卡巴嗪（DTIC）850 mg/m²，第4 - 9天静脉持续输注重组白细胞介素-2（rIL-2）（Cetus公司生产）18×10⁶ IU/m²/天。共进行6个治疗周期：前两个周期间隔13天，后续周期间隔20天。目前有20例患者可进行毒性评估，18例可进行疗效评估。其中2例患者患有转移性眼内黑色素瘤。中位年龄为48岁（范围18 - 83岁），中位卡诺夫斯基指数为100（范围80 - 100）。4例患者曾接受过放疗，1例曾接受过免疫治疗。17例患者接受了两个周期的治疗，9例患者接受了三个或更多周期的治疗。4例患者有反应（22%）：2例完全缓解，2例部分缓解。6例患者病情稳定（33%）。反应出现在肺、皮肤、脾脏和淋巴结。75%的患者在第l周期接受了全剂量的rIL-2，而在第3周期，9例患者中只有2例（22%）接受了计划剂量。rIL-2治疗后24 - 48小时出现5.3×10³/L（范围1.2 - 18.1）的反弹淋巴细胞增多，但这对反应无预测价值。目前，没有证据表明DTIC预处理会对rIL-2刺激的淋巴细胞增殖产生负面影响。该治疗方案的毒性特征与已描述的类似rIL-2方案无显著差异。然而，在这项中期分析中，有更高比例（25%）的患者出现严重体重增加（超过10%）的趋势。本研究表明，该治疗方案对转移性黑色素瘤有效，毒性可接受。进一步研究将集中于联合使用其他化疗药物和/或其他生物反应调节剂（如干扰素、肿瘤坏死因子）与rIL-2。
