Department of Dermatology, Center of Dermatooncology, University of Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.
Cancer Immunol Immunother. 2011 Apr;60(4):487-93. doi: 10.1007/s00262-010-0957-3. Epub 2010 Dec 21.
Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in a subset of advanced patients with melanoma. As we reported previously, intratumoral IL-2 induced complete local responses in more than 60% of melanoma patients. This study aimed to analyze the long-term outcome of 72 patients treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with injectable metastases received intratumoral IL-2 injections thrice weekly at individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose, 72 MIU; median number of injected metastases, 10). The observed 2-year overall survival rates were 95.5% for stage III patients with cutaneous metastases only (stage IIIB), 72% for those with combined cutaneous and lymph node involvement (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft-tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of unresectable distant metastases subsequently received chemotherapy in the further course of disease and showed an overall response rate of 36.7% (16.7% complete responses, 20% partial responses). A high total dose of IL-2 and a dacarbazine/temozolomide-based chemotherapy regimen were variables correlated with a clinical response. In conclusion, patients with cutaneous metastasis without lymph node involvement in stage III and with soft-tissue metastasis without visceral involvement in stage IV showed unexpected favorable survival rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2 treatment seemed to be associated with increased complete and partial responses in subsequent chemotherapies.
全身大剂量白细胞介素-2 (IL-2) 治疗可使部分晚期黑色素瘤患者获得长期生存。正如我们之前报道的,肿瘤内 IL-2 诱导超过 60%的黑色素瘤患者获得完全局部反应。本研究旨在分析两期试验中 72 例患者的长期结果。接受可注射转移灶的黑色素瘤患者(49 例 III 期,23 例 IV 期)每周三次接受肿瘤内 IL-2 注射,剂量逐渐增加(中位持续时间 6.5 周;中位总 IL-2 剂量 72MIU;中位数注射转移灶数为 10)。仅皮肤转移的 III 期患者(III 期 B 期)的 2 年总生存率为 95.5%,皮肤和淋巴结受累的患者(III 期 C 期)为 72%,远处软组织转移局限的 IV 期患者(IV 期 M1a 期)为 66.7%,有内脏转移的患者(IV 期 M1b 和 IV 期 M1c 期)为 9.1%。30 例报告不可切除的远处转移复发的患者随后在疾病进一步发展过程中接受化疗,总缓解率为 36.7%(完全缓解率 16.7%,部分缓解率 20%)。高总剂量的 IL-2 和基于达卡巴嗪/替莫唑胺的化疗方案是与临床反应相关的变量。总之,III 期无淋巴结受累的皮肤转移和 IV 期无内脏受累的软组织转移患者接受肿瘤内 IL-2 治疗后,生存情况出人意料地良好。此外,肿瘤内 IL-2 治疗似乎与随后化疗中完全缓解和部分缓解的增加有关。