Alexandrescu Doru T, Dutcher Janice P, Wiernik Peter H
New York Medical College, Our Lady of Mercy Medical Center, Comprehensive Cancer Center, Bronx, NY 10466, USA.
Med Oncol. 2005;22(2):101-11. doi: 10.1385/mo:22:2:101.
Current treatment options in metastatic melanoma are of limited efficacy. Achievement of durable responses with biological agents, and the possibility to complement the higher response rate of chemotherapy and combined chemotherapy by prolonged duration of responses, led to development of biochemotherapy. Although a clear improvement in response rate (40-60% OR) resulted in some studies of the combined modality, several phase III studies had mixed results on the duration of survival. Various timeframes between the administration of chemotherapy and biologics have been tested, ranging between concurrent biochemotherapy, 1 d (immediately sequential), and up to 3 wk (long sequence or alternating). An analysis of the trend of responses and survival versus the duration of the chemobiotherapy sequence showed that, as the timeframe between chemo and bio components increases, the overall survival, survival of complete responders, and survival of partial responders appear to increase, but the effect is only present for the chemo-bio, and not for the bio-chemo sequence. Because there is no current explanation for this observation, it appears possible that the interaction between components of biochemotherapy results in a double effect: an increase in the immediate response reflected in the OR, CR, PR on one side, and an increase in survival on the other side. An analysis of mechanisms involved in the response leads us hypothesize that macrophage activation, as measured by the neopterin levels, may correlate with the survival of patients undergoing biochemotherapy, while the generation of nitric oxide, acting synergistically with chemotherapy in producing tumor cell killing, may be reflected in the overall response rate seen with the biochemotherapy combinations.
转移性黑色素瘤目前的治疗选择疗效有限。生物制剂能实现持久缓解，且通过延长缓解时间有可能提高化疗及联合化疗的缓解率，从而催生了生物化疗。尽管在一些联合治疗模式的研究中缓解率有明显提高（客观缓解率为40%-60%），但多项III期研究在生存期方面结果不一。化疗和生物制剂给药之间的各种时间间隔都已进行测试，范围从同步生物化疗、1天（立即序贯）到3周（长序贯或交替）。对化疗生物治疗序列持续时间与缓解及生存趋势的分析表明，随着化疗和生物制剂成分之间时间间隔的增加，总生存期、完全缓解者的生存期和部分缓解者的生存期似乎都有所增加，但这种效果仅出现在化疗-生物制剂序列中，而不是生物制剂-化疗序列中。由于目前对此观察结果尚无解释，生物化疗成分之间的相互作用似乎有可能产生双重效果：一方面在客观缓解率、完全缓解率、部分缓解率上体现为即时缓解增加，另一方面生存期增加。对缓解所涉及机制的分析使我们推测，以新蝶呤水平衡量的巨噬细胞激活可能与接受生物化疗患者的生存期相关，而一氧化氮的产生与化疗协同作用导致肿瘤细胞杀伤，可能体现在生物化疗联合方案的总体缓解率上。
