Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia.
Department of Oncology, Child Oncology and Ray Therapy, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.
Oncologist. 2021 May;26(5):364-e734. doi: 10.1002/onco.13761. Epub 2021 Apr 9.
Melatonin did not increase the efficacy of systemic chemotherapy in melanoma. Metformin did not increase the efficacy of systemic chemotherapy in melanoma.
Current data support the possibility of antitumor activity of melatonin and metformin.
From March 2014 to December 2016, 57 patients with disseminated melanoma received dacarbazine (DTIC) 1,000 mg/m on day 1 of a 28-day cycle, either as monotherapy (first group) or in combination with melatonin 3 mg p.o. daily (second group) or metformin 850 mg two times a day p.o. daily (third group) as the first-line of chemotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints were time to progression (TTP), overall survival (OS), immunologic biomarkers, and quality of life.
ORR was 7% and did not differ among the treatment groups. Median TTP was 57, 57, and 47 days, respectively, in the first, second, and third groups (р = .362). Median OS was 236, 422, and 419 days, respectively (p = .712). Two patients from the combinations groups showed delayed response to therapy. The increase of CD3 CD4 HLA-DR lymphocytes (p = .003), CD3 CD8 HLA-DR (p = .045), CD3 CD8 lymphocytes (p = .012), CD4 CD25 CD127 lymphocytes (p = .029), and overall quantity of lymphocytes (p = .021) was observed in patients with clinical benefit.
No benefit was found in either combination over DTIC monotherapy. Delayed responses in melatonin and metformin combination groups were registered. The increase of lymphocyte subpopulations responsible for antitumor immune response demonstrates the immune system's potential involvement in clinical activity.
褪黑素并未提高黑色素瘤患者全身化疗的疗效。二甲双胍并未提高黑色素瘤患者全身化疗的疗效。
目前的数据支持褪黑素和二甲双胍具有抗肿瘤活性的可能性。
从 2014 年 3 月至 2016 年 12 月，57 例转移性黑色素瘤患者接受达卡巴嗪（DTIC）1000mg/m2，每 28 天为一个周期，单药治疗（第 1 组）或联合褪黑素 3mg 口服，每日 1 次（第 2 组）或二甲双胍 850mg，每日 2 次口服（第 3 组）作为一线化疗。主要终点是客观缓解率（ORR）。次要终点是无进展生存期（TTP）、总生存期（OS）、免疫生物标志物和生活质量。
ORR 为 7%，且三组间无差异。第 1、2 和 3 组的中位 TTP 分别为 57、57 和 47 天（p=0.362）。中位 OS 分别为 236、422 和 419 天（p=0.712）。联合组的 2 例患者出现治疗后延迟反应。临床获益患者中观察到 CD3 CD4 HLA-DR 淋巴细胞（p=0.003）、CD3 CD8 HLA-DR（p=0.045）、CD3 CD8 淋巴细胞（p=0.012）、CD4 CD25 CD127 淋巴细胞（p=0.029）和总淋巴细胞数量（p=0.021）增加。
褪黑素和二甲双胍联合治疗并未优于 DTIC 单药治疗。在褪黑素和二甲双胍联合组中观察到延迟反应。负责抗肿瘤免疫反应的淋巴细胞亚群增加表明免疫系统可能参与了临床活性。
