Punt C J A, Suciu S, Gore M A, Koller J, Kruit W H J, Thomas J, Patel P, Lienard D, Eggermont A M M, Keilholz U
Department of Medical Oncology, St. Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Eur J Cancer. 2006 Nov;42(17):2991-5. doi: 10.1016/j.ejca.2006.08.012. Epub 2006 Oct 4.
Chemoimmunotherapy for patients with metastatic melanoma is associated with high toxicity, and only a subset of patients will benefit. This randomised phase II study was performed with the primary objective of exploring whether two cycles of dacarbazine monotherapy could select the subset of patients that would benefit most from more intensive chemoimmunotherapy.
Patients with metastatic melanoma were randomised to either receive chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha and interleukin-2 (arm A) or initial treatment with two cycles of dacarbazine monotherapy followed irrespective of response by the same 4-drug regimen of chemoimmunotherapy (arm B). Chemoimmunotherapy was continued in the absence of disease progression for a maximum of four cycles. Primary end-point was the disease stabilisation rate.
A total of 93 patients were randomised, and 89 patients were eligible. Disease stabilisation (complete/partial response or stable disease) was achieved in 19 patients (42.2%) in arm A and 9 patients (20.5%) in arm B. In arm B 32 of the 44 patients continued chemoimmunotherapy after two cycles of dacarbazine. Of 20 patients with progressive disease (PD) after two cycles of dacarbazine in arm B, only 2 patients achieved an objective response. Median overall survival (OS) in arms A and B was 10.5 months and 9.5 months, respectively.
Despite a lower initial stabilisation rate, the strategy of starting with 2 courses of DTIC prior to a 4-drug regimen led to comparable median overall survival. Only few transient responses were achieved with the 4-drug regimen in patients with disease progression on DTIC, suggesting frequent cross resistance. Two cycles of dacarbazine monotherapy cannot be recommended to select patients for more intensive chemoimmunotherapy.
转移性黑色素瘤患者的化疗免疫疗法毒性高，只有部分患者能从中获益。本随机II期研究的主要目的是探索达卡巴嗪单药治疗两个周期是否能筛选出最能从更强化的化疗免疫疗法中获益的患者亚组。
转移性黑色素瘤患者被随机分为两组，一组接受达卡巴嗪、顺铂、α干扰素和白细胞介素-2的化疗免疫疗法（A组），另一组先接受两个周期的达卡巴嗪单药初始治疗，无论反应如何，随后接受相同的4药联合化疗免疫疗法（B组）。在疾病无进展的情况下，化疗免疫疗法最多持续四个周期。主要终点是疾病稳定率。
共93例患者被随机分组，89例符合条件。A组19例患者（42.2%）实现疾病稳定（完全/部分缓解或疾病稳定），B组9例患者（20.5%）实现疾病稳定。B组44例患者中有32例在两个周期的达卡巴嗪治疗后继续接受化疗免疫疗法。B组中20例在两个周期的达卡巴嗪治疗后出现疾病进展（PD）的患者中，只有2例获得客观缓解。A组和B组的中位总生存期（OS）分别为10.5个月和9.5个月。
尽管初始稳定率较低，但在4药联合方案之前先进行2个疗程达卡巴嗪的治疗策略导致中位总生存期相当。对于达卡巴嗪治疗后疾病进展的患者，4药联合方案仅产生少数短暂缓解，提示频繁交叉耐药。不建议采用两个周期的达卡巴嗪单药治疗来筛选患者进行更强化的化疗免疫疗法。
