Department of Medicine, Karolinska Institutet, Nobels Väg 6, Stockholm, 171 76, Sweden.
Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Eugeniavägen 12, Stockholm, 171 64, Sweden.
Trials. 2023 Mar 26;24(1):230. doi: 10.1186/s13063-023-07245-9.
Uveal melanoma is the most common primary intraocular tumor in adults. In Sweden, at least 100 patients are diagnosed with the disease each year. Almost half of the patients develop metastases, with a median survival time of 1 year once metastases are detected. The primary ocular tumor is typically treated with either enucleation or brachytherapy, and no adjuvant treatment is added. Melatonin is an indolamine hormone that has improved survival in previous trials with patients diagnosed with various cancers, including advanced cutaneous melanoma. Side effects have been mild. We aim to investigate if adjuvant treatment with melatonin for 5 years following diagnosis of non-metastasized uveal melanoma can decrease the occurrence of metastases.
An open-label, prospective, 5-year randomized clinical trial (RCT) will be conducted at St. Erik Eye Hospital. One hundred patients recently diagnosed with non-metastatic uveal melanoma will be randomized to either treatment with adjuvant melatonin 20 mg (4 tablets of 5 mg) at 10 pm for 5 years, or to standard follow-up (control group). The primary outcome measurement is the relative risk for having developed metastases 5 years after randomization. The secondary outcomes are overall survival, risk of developing other cancers, overall survival after detection of metastases, and differences in the occurrence of adverse events (AE) and serious adverse events (SAE) between the groups.
Melatonin has been found to positively impact our immune system, inhibit angiogenesis, stimulate apoptosis in malignant cells, and act as a potent antioxidant. Previous clinical trials have used similar doses of melatonin with positive results, particularly in advanced stages of cancer. Previous animal and human studies have found the toxicity of the hormone to be low. Considering the potential benefits and limited risks of melatonin, as well as its global availability, it may be a suitable candidate for an adjuvant treatment in patients with uveal melanoma.
Our trial protocol has been approved and registered by the Swedish Medical Products Agency on June 22, 2022 (EudraCT 2022-500,307-49-00). Our trial registration number is NCT05502900, and the date of registration is August 16, 2022.
葡萄膜黑素瘤是成年人中最常见的原发性眼内肿瘤。在瑞典，每年至少有 100 名患者被诊断出患有该病。几乎一半的患者会发生转移，一旦发生转移，中位生存时间为 1 年。原发性眼内肿瘤通常采用眼球摘除术或近距离放射治疗，不添加辅助治疗。褪黑素是一种吲哚胺激素，在先前针对包括晚期皮肤黑素瘤在内的各种癌症患者的试验中提高了生存率。副作用较轻。我们旨在研究诊断为非转移性葡萄膜黑素瘤后 5 年内使用褪黑素辅助治疗是否可以降低转移的发生。
这项研究将在圣埃里克眼科医院开展一项开放标签、前瞻性、5 年随机临床试验（RCT）。100 名最近被诊断为非转移性葡萄膜黑素瘤的患者将被随机分为辅助治疗组（接受每晚 10 点口服褪黑素 20mg[4 片 5mg 片剂]，共 5 年）或标准随访组（对照组）。主要结局测量指标为随机分组后 5 年内发生转移的相对风险。次要结局包括总生存率、发生其他癌症的风险、发生转移后的总生存率以及两组间不良事件（AE）和严重不良事件（SAE）发生的差异。
褪黑素已被发现可对我们的免疫系统产生积极影响，抑制血管生成，刺激恶性细胞凋亡，并作为一种有效的抗氧化剂。先前的临床试验使用了类似剂量的褪黑素，结果均为阳性，尤其是在癌症晚期。先前的动物和人体研究发现该激素的毒性较低。考虑到褪黑素的潜在益处和有限风险，以及其在全球范围内的可获得性，它可能是葡萄膜黑素瘤患者辅助治疗的合适候选药物。
我们的试验方案已于 2022 年 6 月 22 日获得瑞典药品管理局的批准和注册（EudraCT 2022-500,307-49-00）。我们的试验注册号为 NCT05502900，登记日期为 2022 年 8 月 16 日。
