Hersey P
Department of Immunology and Oncology, Newcastle Mater Misericordiae Hospital, NSW, Australia.
Ann N Y Acad Sci. 1993 Aug 12;690:167-77. doi: 10.1111/j.1749-6632.1993.tb44006.x.
Patients who develop metastases from melanoma in regional lymph nodes are known to be at high risk of developing further recurrences after surgical removal of the lymph node metastases. This study examines whether immunization over a two-year period with a vaccine made from vaccinia viral lysates of an allogeneic melanoma cell (VMCL), following surgical removal of lymph node metastases, would help prevent the development of distant metastases and improve survival from the disease. Eighty patients treated with VMCL alone and followed for a minimum of 5.5 years had improved survival compared with that of a historical control group of 151 patients and a concurrent nonrandomized group of 55 patients. Similarly, survival of 102 patients treated with VMCL plus low dose cyclophosphamide for a minimum of 3.5 years was superior to that of the historical control group but not to that of the group treated with VMCL alone. Improvement in survival measured from the date of removal of the primary tumor was still evident. Analysis of subsets of patients showed that VMCL treatment appeared to benefit patients irrespective of the number of lymph nodes involved and whether surgery was carried out near to (synchronous metastases) or some time after removal of the primary (delayed metastases). Analysis of two additional aspects provided further evidence for a biologic effect of the vaccine. One was an apparent alteration in distribution of metastases with a lower incidence of cutaneous metastases relative to visceral metastases in VMCL-treated patients. The second was a change in time to development of recurrences with a higher proportion of metastases occurring after 2 years in the treated patients. Of a projected 400 patients, 384 were entered into a randomized control (phase III) study to further evaluate this treatment. An interim analysis gave no reason for premature closure of the trial. This next analysis is scheduled for 9 months after closure of the trial.
已知在区域淋巴结发生黑色素瘤转移的患者，在手术切除淋巴结转移灶后有很高的进一步复发风险。本研究旨在探讨在手术切除淋巴结转移灶后，用一种由同种异体黑色素瘤细胞的痘苗病毒裂解物制成的疫苗进行为期两年的免疫接种，是否有助于预防远处转移的发生并提高该疾病的生存率。单独接受VMCL治疗并随访至少5.5年的80例患者，与151例历史对照组患者和55例同期非随机组患者相比，生存率有所提高。同样，接受VMCL加低剂量环磷酰胺治疗至少3.5年的102例患者的生存率优于历史对照组，但不如单独接受VMCL治疗的组。从原发肿瘤切除日期开始测量的生存率改善仍然明显。对患者亚组的分析表明，无论受累淋巴结的数量以及手术是在切除原发灶附近（同步转移）还是在切除原发灶一段时间后（延迟转移）进行，VMCL治疗似乎都对患者有益。对另外两个方面的分析为疫苗的生物学效应提供了进一步的证据。一是转移分布的明显改变，在接受VMCL治疗的患者中，皮肤转移的发生率相对于内脏转移较低。二是复发发生时间的变化，在接受治疗的患者中，2年后发生转移的比例更高。在预计的400例患者中，384例进入了随机对照（III期）研究，以进一步评估这种治疗方法。中期分析没有理由提前终止试验。下一次分析计划在试验结束后9个月进行。
