Flaherty L E, Redman B G, Chabot G G, Martino S, Gualdoni S M, Heilbrun L K, Valdivieso M, Bradley E C
Department of Internal Medicine, Harper Hospital, Wayne State University School of Medicine, Detroit, Michigan 48201.
Cancer. 1990 Jun 1;65(11):2471-7. doi: 10.1002/1097-0142(19900601)65:11<2471::aid-cncr2820651113>3.0.co;2-f.
Because of encouraging response rates published with recombinant interleukin-2 (rIL-2) alone in metastatic malignant melanoma (MMM), dacarbazine (DTIC) and rIL-2 were sequentially combined to evaluate efficacy, toxicity, pharmacokinetics, and immunologic interaction. Thirty-two patients aged 18 to 67 years have received 127 courses of treatment. The dose of DTIC was 1.0 g/m2 as a 24-hour infusion every 28 days on day 1. Recombinant interleukin-2 (2.0, 3.0, 4.0, or 5.0 x 10(6) Cetus units/m2) was administered as a 30-minute infusion on days 15 through 19 and 22 through 26 of each 28-day cycle. Seven of 32 patients (22%) who received therapy had a remission, one complete and six partial. The complete response was in a lung mass. Partial responses were seen in lymph nodes, liver, and lung. The median duration of response was 4.7 months. One patient is in persistent partial remission of the liver for greater than 2 years. One patient had residual mediastinal disease resected after partial response and remains without evidence of disease for 18+ months. This regimen was generally well tolerated, did not create overlapping toxicity, and produced encouraging responses in visceral sites. This provides a framework for future combinations of chemotherapy with rIL-2 alone or in combination with other biologic response modifiers in an outpatient setting.
由于单独使用重组白细胞介素-2（rIL-2）治疗转移性恶性黑色素瘤（MMM）已公布的令人鼓舞的缓解率，故将达卡巴嗪（DTIC）与rIL-2序贯联合使用，以评估疗效、毒性、药代动力学和免疫相互作用。32例年龄在18至67岁的患者接受了127个疗程的治疗。DTIC的剂量为1.0 g/m²，每28天的第1天进行24小时输注。重组白细胞介素-2（2.0、3.0、4.0或5.0×10⁶ Cetus单位/m²）在每个28天周期的第15至19天和第22至26天进行30分钟输注。接受治疗的32例患者中有7例（22%）出现缓解，1例完全缓解，6例部分缓解。完全缓解发生在肺部肿块。部分缓解见于淋巴结、肝脏和肺部。缓解的中位持续时间为4.7个月。1例患者肝脏持续部分缓解超过2年。1例患者在部分缓解后切除了残留的纵隔病变，且18多个月来无疾病证据。该方案总体耐受性良好，未产生重叠毒性，在内脏部位产生了令人鼓舞的反应。这为未来在门诊环境中单独使用rIL-2或与其他生物反应调节剂联合进行化疗组合提供了一个框架。
