Lopez M, Carpano S, Cavaliere R, Di Lauro L, Ameglio F, Vitelli G, Frasca A M, Vici P, Pignatti F, Rosselli M
Regina Elena Institute for Cancer Research, Rome, Italy.
Ann Oncol. 1994 Oct;5(8):741-6. doi: 10.1093/oxfordjournals.annonc.a058979.
DTIC and interleukin-2 (IL-2), as single agents, have a limited anti-tumor activity in patients with metastatic melanoma. Experimentally, thymosin alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and immunological effects of a combination with these three agents.
Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3 weeks.
Objective responses were obtained in 15 (36%) of 42 evaluable patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and stable disease was observed in five. The median time to progression was 5.5 months and median survival was 11 months. Side effects were predominantly caused by IL-2. Treatment was tolerated reasonably well, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Baseline sCD4 levels seem to correlate to tumor burden. Patients benefiting from treatment had lower sCD4 and higher sCD8 than did progressing patients.
The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.
达卡巴嗪（DTIC）和白细胞介素-2（IL-2）作为单一药物，对转移性黑色素瘤患者的抗肿瘤活性有限。实验表明，胸腺肽α1（TA1）可能调节IL-2的作用。我们研究了这三种药物联合使用的临床和免疫学效果。
46例可测量的转移性黑色素瘤患者在第1天接受静脉注射850 mg DTIC治疗，第4至7天接受皮下注射2 mg TA1治疗，第8至12天通过持续静脉输注接受18 MU/m²/d的IL-2治疗。每3周重复一个周期。
42例可评估患者中有15例（36%）获得客观缓解（95%置信区间：22%-50%）。2例患者出现完全缓解，5例患者病情稳定。中位进展时间为5.5个月，中位生存期为11个月。副作用主要由IL-2引起。治疗耐受性良好，化疗和生物治疗之间没有重叠毒性或相互干扰。基线可溶性CD4水平似乎与肿瘤负荷相关。从治疗中获益的患者比病情进展的患者sCD4水平更低，sCD8水平更高。
DTIC + TA1 + IL-2联合方案在晚期黑色素瘤治疗中具有活性，毒性可接受。然而，仍需要更有效的方案，并且胸腺激素与细胞因子之间的相互作用应进一步探索。
