Livingston P O, Wong G Y, Adluri S, Tao Y, Padavan M, Parente R, Hanlon C, Calves M J, Helling F, Ritter G
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Clin Oncol. 1994 May;12(5):1036-44. doi: 10.1200/JCO.1994.12.5.1036.
To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction.
One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy).
GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance.
(1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.
对美国癌症联合委员会（AJCC）III期黑色素瘤患者进行一项双盲随机试验，原因如下：（1）证实我们之前的发现，即携带黑色素瘤分化抗原GM2抗体的患者预后改善；（2）证明GM2抗体诱导带来的临床益处。
122例AJCC III期黑色素瘤患者术后无疾病，被随机分组：58例接受GM2/卡介苗（BCG）疫苗治疗，64例仅接受卡介苗（BCG）治疗。所有患者均先用低剂量环磷酰胺（Cy）预处理。
58例接受GM2/BCG治疗的患者中有50例检测到GM2抗体，64例仅接受BCG治疗的患者中有7例检测到GM2抗体。在至少随访51个月时，这57例抗体阳性患者的无病间期显著延长（P = 0.004），总生存期增加17%（P = 0.02），证实了我们早期的经验。将所有预先存在GM2抗体的患者（GM2/BCG组1例，BCG组5例）排除在统计分析之外，接受GM2/BCG疫苗治疗的患者在51个月时无病间期增加23%（P = 0.02），总生存期增加14%（P = 0.15）。然而，当将两个治疗组的所有患者按随机分组情况进行比较时，GM2/BCG治疗组的无病间期增加18%，生存期增加11%，两者均无统计学意义。
（1）GM2/BCG疫苗接种在大多数患者中诱导产生免疫球蛋白M（IgM）抗体。（2）GM2抗体产生与延长无病间期和生存期相关。（3）该试验随机分组的两组比较未显示GM2/BCG疫苗治疗的患者在无病间期或生存期有统计学意义的改善。
