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Abstract：
BACKGROUND: Primary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial.
METHODS: A 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and 18F-fluoro-deoxyglucose positron emission tomography (FDG/PET)-computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET-CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months.
CONCLUSIONS: The findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.
METHODS: A 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and 18F-fluoro-deoxyglucose positron emission tomography (FDG/PET)-computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET-CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months.
CONCLUSIONS: The findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.
摘要：
背景：原发性阴道恶性黑色素瘤极为罕见，预后比皮肤恶性黑色素瘤差。以前的研究已经探索了伊曲康唑的再利用，一种常见的口服抗真菌剂，用于治疗各种癌症。这里,我们描述了一个转移性患者，在一项临床机会窗试验中，口服200mg伊曲康唑每天两次治疗不可切除的阴道恶性黑色素瘤。
方法：一名患有阴道和腹股沟肿瘤的64岁日本妇女被转诊到我们的机构。根据阴道癌转移到腹股沟淋巴结的初步诊断，我们在一项临床试验中对她进行了伊曲康唑治疗,直至获得活检和影像学检查结果.在此期间,进行了三次活检，和18F-氟-脱氧葡萄糖正电子发射断层扫描（FDG/PET）-计算机断层扫描（CT）进行了两次。活检结果证实了阴道原发性恶性黑色素瘤的诊断。影像学研究显示转移到多个部位，包括大脑,为此她接受了伽玛刀治疗.在nivolumab开始之前的窗口期，患者接受伊曲康唑治疗30天.伊曲康唑开始后一周内，腹股沟淋巴结疼痛得到改善.第6天和第30天的PET-CT显示肿瘤大小和FDG摄取减少，分别。对第1、13和30天获得的活检标本进行cDNA微阵列分析，这揭示了四个基因转录的100倍下调：STATH，EEF1A2,TTR,和CDH2。纳武单抗给药12周后，她发展为进行性疾病和3级免疫相关性肝炎。停用nivolumab导致左骨盆和腹股沟疼痛的发生。在用伊曲康唑再次攻击后，患者4个月没有报告任何疼痛。
结论：本病例的研究结果表明，伊曲康唑是原发性阴道恶性黑色素瘤的潜在有效治疗选择。此外，我们确定了潜在的伊曲康唑靶基因，这可能有助于阐明这种疾病的潜在机制，并可能有助于开发新的治疗药物。
方法：一名患有阴道和腹股沟肿瘤的64岁日本妇女被转诊到我们的机构。根据阴道癌转移到腹股沟淋巴结的初步诊断，我们在一项临床试验中对她进行了伊曲康唑治疗,直至获得活检和影像学检查结果.在此期间,进行了三次活检，和18F-氟-脱氧葡萄糖正电子发射断层扫描（FDG/PET）-计算机断层扫描（CT）进行了两次。活检结果证实了阴道原发性恶性黑色素瘤的诊断。影像学研究显示转移到多个部位，包括大脑,为此她接受了伽玛刀治疗.在nivolumab开始之前的窗口期，患者接受伊曲康唑治疗30天.伊曲康唑开始后一周内，腹股沟淋巴结疼痛得到改善.第6天和第30天的PET-CT显示肿瘤大小和FDG摄取减少，分别。对第1、13和30天获得的活检标本进行cDNA微阵列分析，这揭示了四个基因转录的100倍下调：STATH，EEF1A2,TTR,和CDH2。纳武单抗给药12周后，她发展为进行性疾病和3级免疫相关性肝炎。停用nivolumab导致左骨盆和腹股沟疼痛的发生。在用伊曲康唑再次攻击后，患者4个月没有报告任何疼痛。
结论：本病例的研究结果表明，伊曲康唑是原发性阴道恶性黑色素瘤的潜在有效治疗选择。此外，我们确定了潜在的伊曲康唑靶基因，这可能有助于阐明这种疾病的潜在机制，并可能有助于开发新的治疗药物。
