Endocrinology and Nutrition Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Endocrinology and Nutrition Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
Front Endocrinol (Lausanne). 2023 Aug 31;14:1204206. doi: 10.3389/fendo.2023.1204206. eCollection 2023.
Current guidelines recommend temozolomide as the first-line chemotherapy for aggressive pituitary neuroendocrine tumours. However, no clinical trials have been conducted to date and clinical experience is quite limited. We retrospectively analyzed 28 patients (9 women and 19 men), aged 46.6 + 16.9, with aggressive pituitary tumours (4 pituitary carcinomas and 24 aggressive adenomas) treated with temozolomide in 10 Spanish pituitary reference centres. Four patients had Cushing's disease, 9 prolactinomas and 15 clinically non-functioning pituitary tumours (seven silent corticotroph, three silent somatotroph, one silent lactotroph, one silent gondotroph and three null-cell tumours). Median size at diagnosis was 10.5 cm3 (IQR 4.7-22.5), with cavernous sinus invasion in 88% and no metastases. Pre-temozolomide treatment, these data were 5.2 cm3 (IQR 1.9-12.3), 89.3% and 14.3% (2 intracranial and 2 spinal metastases). All patients had undergone surgery (1-5 surgeries), 25 (89.3%) had received radiotherapy (7 of them reirradiated) and 13(46.4%) had received cabergoline. One patient interrupted temozolomide prematurely. The remaining 27 patients received a median of 13 cycles (range 3-66) of 5 days every 28 days, with a mean initial dose of 265 ± 73 mg when administered alone and of 133 ± 15 mg when co-administered with radiotherapy. Eight patients (29.6%) had a significant reduction (>30%) in tumour volume and 14 (51.9%) attained tumour stabilization. After a median follow-up of 29 months (IQR 10-55), 8 out of these 22 showed disease progression. A longer progression-free survival was found in the five patients who received concomitant radiotherapy. Seven patients (25%) died (all of them because of tumour progression or complications of treatments) at 77 months (IQR 42-136) after diagnosis and 29 months (IQR 16-55) after the first dose of temozolomide. Adverse effects occurred in 18 patients (14 mild and 4 moderate or severe). In conclusion, temozolomide is an effective medical treatment for aggressive pitNET and pituitary carcinomas but is sometimes followed by tumour progression. Co-administration with radiotherapy may increase progression-free survival.
目前的指南建议替莫唑胺作为侵袭性垂体神经内分泌肿瘤的一线化疗药物。然而，迄今为止，尚未进行临床试验，临床经验相当有限。我们回顾性分析了 10 家西班牙垂体参考中心治疗的 28 例（9 名女性和 19 名男性）侵袭性垂体肿瘤（4 例垂体癌和 24 例侵袭性腺瘤）患者，年龄 46.6±16.9 岁。4 例患者患有库欣病，9 例催乳素瘤，15 例临床无功能垂体肿瘤（7 例无功能促肾上腺皮质激素瘤，3 例无功能生长激素瘤，1 例无功能催乳素瘤，1 例无功能促性腺激素瘤和 3 例无功能细胞瘤）。中位诊断时肿瘤大小为 10.5cm3（IQR 4.7-22.5），海绵窦侵犯率为 88%，无转移。在替莫唑胺治疗前，这些数据分别为 5.2cm3（IQR 1.9-12.3）、89.3%和 14.3%（2 例颅内转移和 2 例脊髓转移）。所有患者均接受了手术治疗（1-5 次手术），25 例（89.3%）接受了放疗（其中 7 例再次放疗），13 例（46.4%）接受了卡麦角林治疗。1 例患者提前中断了替莫唑胺治疗。其余 27 例患者接受了中位数为 13 个周期（范围 3-66）的 5 天/28 天治疗，初始平均剂量为 265±73mg，单独使用时为 265±73mg，与放疗联合使用时为 133±15mg。8 例（29.6%）患者肿瘤体积显著缩小（>30%），14 例（51.9%）患者肿瘤稳定。在中位随访 29 个月（IQR 10-55）后，22 例中有 8 例出现疾病进展。在接受同步放疗的 5 例患者中，无进展生存期较长。7 例（25%）患者在诊断后 77 个月（IQR 42-136）和替莫唑胺首次治疗后 29 个月（IQR 16-55）因肿瘤进展或治疗相关并发症死亡。18 例患者出现不良反应（14 例为轻度，4 例为中度或重度）。总之，替莫唑胺是侵袭性垂体神经内分泌肿瘤和垂体癌的有效治疗方法，但有时会导致肿瘤进展。与放疗联合应用可能会增加无进展生存期。
