Sequential dacarbazine chemotherapy followed by recombinant interleukin-2 in metastatic melanoma. A pilot multicentre phase I-II study.

E Shiloni, P Pouillart, J Janssens, T Splinter, T Di Peri, M Symann, G J Roest, P A Palmer, C R Franks
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Abstract

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.

顺序达卡巴嗪化疗后重组白介素-2治疗转移性黑色素瘤。一项多中心I-II期试验研究。
1988年4月至1989年8月,30例黑色素瘤患者进入了一项多中心II期研究,第1天给予达卡巴嗪(DTIC) 850 mg/m2静脉注射,第4-9天连续静脉注射重组白细胞介素-2 (il -2) 18 × 10(6) IU/m2/天静脉注射。给予6个治疗周期:前两个周期间隔13天,后两个周期间隔20天。目前有20例患者可评估毒性,18例可评估反应。其中两名患者表现为转移性眼内黑色素瘤。年龄中位数为48岁(范围18-83),Karnofsky指数中位数为100(范围80-100)。4例患者先前接受过放疗,1例患者先前接受过免疫治疗。17名患者接受了两个疗程的治疗,9名患者接受了三个或更多疗程的治疗。4例患者缓解(22%):2例完全缓解,2例部分缓解。6例(33%)患者病情稳定。反应发生在肺、皮肤、脾脏和淋巴结。75%的患者在第一个周期内接受了全剂量的rIL-2,而在第三个周期中只有2 / 9(22%)的患者接受了计划剂量。il -2后24-48小时出现5.3 × 10(3)/L(范围1.2-18.1)的反弹淋巴细胞增多,但不能预测反应。目前,没有证据表明DTIC预处理对ril -2刺激的淋巴细胞增殖有负面影响。该治疗方案的毒性特征与已经描述的类似rIL-2方案没有显着差异。然而,在这个中期分析中,有更高比例的患者(25%)出现严重体重增加(大于10%)的趋势。本研究表明,这种治疗方案对转移性黑色素瘤有效,毒性可接受。进一步的研究将集中于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il -2联合使用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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