O'Brien G C, Cahill R A, Bouchier-Hayes D J, Redmond H P
Dept of Academic Surgery, Cork University Hospital and NUI.
Ir J Med Sci. 2006 Jan-Mar;175(1):10-4. doi: 10.1007/BF03168992.
Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness.
Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response.
Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease.
Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.
重组白细胞介素-2(rIL-2)治疗转移性黑色素瘤受到毒性的限制,尤其是血管渗漏综合征(VLS)。在实验环境中,牛磺罗定可增强IL-2的抗肿瘤作用,同时减少其相关的内皮细胞功能障碍。我们推测,rIL-2与牛磺罗定联合使用可提高耐受性而不削弱疗效。
11例进展性转移性黑色素瘤患者接受高剂量rIL-2并联合输注牛磺罗定。监测患者毒性的发生情况及反应证据。
10例患者耐受了29个疗程的高剂量rIL-2,无需减量。大多数毒性为低级别。无患者发生VLS。7例患者死于疾病进展。2例患者对治疗有完全的临床和影像学反应。2例患者尽管在诊断为转移性疾病后平均17.5个月有疾病进展的证据,但仍存活。
在IV期黑色素瘤患者中,牛磺罗定与高剂量rIL-2联合使用似乎可大大提高该方案的耐受性,而不降低其治疗价值。