Melanoma Program, The Angeles Clinic and Research Institute, 2001 Santa Monica Blvd, Suite 560 W, Santa Monica, CA 90404, USA.
J Clin Oncol. 2009 Dec 20;27(36):6207-12. doi: 10.1200/JCO.2008.20.3075. Epub 2009 Nov 16.
Biochemotherapy improves responses in metastatic melanoma, but not overall survival, in randomized trials. We developed a maintenance biotherapy regimen after induction biochemotherapy in an attempt to improve durability of responses and overall survival.
One hundred thirty-three chemotherapy-naïve patients with metastatic melanoma without CNS metastases were treated at 10 melanoma centers. The biochemotherapy induction regimen included cisplatin, vinblastine, dacarbazine, decrescendo interleukin-2 (IL-2), and interferon alfa-2b with granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine support. Patients not experiencing disease progression were eligible for maintenance biotherapy with low-dose IL-2 and GM-CSF followed by intermittent pulses of decrescendo IL-2 over 12 months. Patients were observed for response, progression-free survival, toxicity, and overall survival.
The response rate to induction biochemotherapy was 44% (95% CI, 35% to 52%; complete response, 8%; partial response, 36%; stable disease, 29%). The median number of biochemotherapy cycles was four, and the median number of maintenance biotherapy cycles was five. The median progression-free survival was 9 months, and the median survival was 13.5 months. The 12-month and 24-month survival rates were 57% and 23%, respectively. Twenty percent of patients remain alive (12 without disease), with median follow-up of 30 months (95% CI, 25+ to 45+ months). Thirty-nine percent of patients developed CNS metastases. The median times to CNS progression and death were 8 months and 5 months, respectively.
Maintenance biotherapy after induction biochemotherapy seems to prolong progression-free survival and improve overall survival compared with recent multicenter trials of biochemotherapy or chemotherapy. The regimen should be studied in a randomized clinical trial in patients with advanced metastatic melanoma. CNS progression remains a formidable challenge.
生物化学疗法可提高转移性黑色素瘤的反应率，但不能提高随机试验的总生存率。我们在诱导生物化学疗法后制定了维持性生物疗法方案，试图提高反应的持久性和总生存率。
133 例无中枢神经系统转移的初治转移性黑色素瘤患者在 10 个黑色素瘤中心接受治疗。生物化学诱导方案包括顺铂、长春碱、达卡巴嗪、递减白细胞介素-2（IL-2）和干扰素 alfa-2b 联合粒细胞巨噬细胞集落刺激因子（GM-CSF）细胞因子支持。无疾病进展的患者有资格接受低剂量 IL-2 和 GM-CSF 维持性生物治疗，然后在 12 个月内间歇性给予递减 IL-2 脉冲。观察患者的反应、无进展生存期、毒性和总生存期。
诱导生物化学疗法的反应率为 44%（95%CI，35%至 52%；完全缓解率为 8%；部分缓解率为 36%；稳定疾病率为 29%）。生物化学疗法的中位数周期数为 4 个，维持性生物疗法的中位数周期数为 5 个。无进展生存期的中位数为 9 个月，总生存期的中位数为 13.5 个月。12 个月和 24 个月的生存率分别为 57%和 23%。20%的患者仍存活（12 例无疾病），中位随访时间为 30 个月（95%CI，25+至 45+个月）。39%的患者发生中枢神经系统转移。中枢神经系统进展和死亡的中位时间分别为 8 个月和 5 个月。
与最近的生物化学疗法或化学疗法的多中心试验相比，诱导生物化学疗法后进行维持性生物疗法似乎可延长无进展生存期并提高总生存率。该方案应在晚期转移性黑色素瘤患者的随机临床试验中进行研究。中枢神经系统进展仍然是一个巨大的挑战。
