四十六位第三期黑色素瘤病患參與AVEMAR對惡性黑色素瘤的臨床研究，其中二十四位對照組僅接受標準治療，另二十二名患者於標準治療外還使用AVEMAR作為輔助治療。結果顯示有使用AVEMAR的腫瘤惡化相關事件發生明顯減少，包括原發腫瘤復發率、淋巴結轉移復發率、新淋巴結轉移、遠距（臟器）轉移的發展。有使用AVEMAR之患者的無惡化時間間隔平均為三百零六天，而於未使用AVEMAR的對照組則是二百一十三天。有使用AVEMAR的無遠距轉移發生的平均時間是三百四十天，而AVEMAR的對照組則是二百五十五天。
| 飲用AVEMAR 第三期黑色素瘤之腫瘤惡化相關事件發生率的影響 |
|
使用 (22 人次) |
未使用 (24人次) |
| 數目 |
百分比 |
數目 |
百分比 |
| 原發腫瘤復發數 |
1 |
4.5 % |
1 |
4.2 % |
| 節腫瘤復發數 |
1 |
4.5 % |
9 |
37.5 % |
| 新節腫瘤發生數 |
3 |
13.6 % |
9 |
37.5 % |
| 第一遠距轉移發生數 |
5 |
22.7 % |
14 |
58.3 % |
| 延伸遠距轉移發生數 |
0 |
0 % |
5 |
20.8 % |
| 整體事件發生數 |
10 |
- |
38 |
- |
| 腫瘤惡化病患人數 |
8 |
36.3 % |
18 |
75.0 % |
|
根據這些結果，使用AVEMAR作為治療第三期黑色素瘤的補充治療能降低腫瘤惡化比例。
Locoregional metastases (stage III) are considered a crucial stage in treatment of melanoma. A complete resection of positive lymph nodes should be performed, though the isolated perfusion of in-transit metastases and/or inoperable primary tumors of the extremities through the use of melphalan or tumor necrosis factor (TNFα) represents another therapeutic approach. However, as the facilities needed for such treatment are available in very few centers, most patients choose radiotherapy treatment. Systemic adjuvant chemotherapy is recommended after a complete resection, but there is as yet no standard accepted form of such therapy. Nevertheless, the basic component of all chemotherapy is Dacarbazine, and no combination of cytostatic drugs has proven more effective than Dacarbazin monotherapy.
Considering the poor efficacy of standard therapy, it is particularly noteworthy that the application of Avemar as a supportive therapy enhanced the effect of Dacarbazine therapy in stage III melanoblastoma. Demidov and his colleagues, after an average observation period of 12 months for a group of 46 stage III melanoma patients (24 standard, 22 standard + Avemar), reported a significant decrease in progression-related events (recurrence of the primary tumor, recurrence of lymph node metastases, new lymph node metastases, development of distant (visceral) metastases) in the Avemar group. The average progression-free interval was 306 days for the Avemar group versus 213 for the control group. The average length of time without distant metastases was 340 days for the Avemar group versus 255 for the control group. The number of progression-related events was 10 for the Avemar group versus 38 for the control group.
No new distant metastases developed in the Avemar group, as compared with 5 in the control patients. There was one recurrent lymph node metastasis in the Avemar group compared with 9 in the control group. Therefore, the use of Avemar as a supportive therapy reduced the overall risk of progression- related events by 52.2%. From this data, the application of Avemar as a complementary treatment in stage III melanoma should be strongly recommended.
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Cumulative progression-free survival probability curves of melanoma patients (Kaplan-Meier estimation)
Progression-related events (end-points analysis) in stage III melanoma patients (Fisher’s exact test)
|
Avemar (n=22) |
Control (n=24) |
| NO |
% |
NO |
% |
Primary disease
recurrence1 |
1 |
4.5 |
1 |
4.2 |
Nodal disease
recurrence2 |
1 |
4.5 |
9 |
37.5 |
New nodal disease
occurrence3 |
3 |
13.6 |
9 |
37.5 |
First distant
metastasis occurrence4 |
5 |
22.7 |
14 |
58.3 |
Further distant
metastasis occurrence5 |
0 |
0 |
5 |
20.8 |
| Overall events |
10 |
- |
38 |
- |
Patients with
progressive disease6 |
8 |
36.3 |
18 |
75.0 |
|
1Not significant difference (ND) (P=0.733); 2P<0.0; 3ND (P=0.065); 4P<0.05; 5P<0.05; 6P<0.01
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