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，到目前为止还没有进行过临床试验，临床经验也非常有限。我们回顾性分析了28名患有侵袭性垂体肿瘤（4例垂体癌和24例侵袭性腺瘤）的患者（9名女性和19名男性），年龄为46.6+16.9岁，他们在西班牙的10个垂体参考中心接受了替莫唑胺治疗。其中4例患有库欣病，9例患有催乳素瘤，15例临床无功能性垂体肿瘤（七例沉默性变质细胞瘤，三例沉默性生长激素细胞瘤，一例沉默性泌乳激素细胞瘤，一例沉默性性腺激素细胞瘤和三例零细胞瘤）。诊断时的中位肿瘤体积为10.5 cm3（IQR 4.7-22.5），其中88%有海绵窦浸润而无转移。在接受替莫唑胺治疗前，这些数据为5.2 cm3（IQR 1.9-12.3），89.3%和14.3%（头颅内2例和脊髓内2例转移）。所有患者均已接受手术（1-5次手术），25名患者（89.3%）接受放疗（其中7例再次接受放疗），13名患者（46.4%）接受卡贝果林治疗。其中一名患者中断了替莫唑胺的治疗。其余27名患者接受了中位的13个疗程（范围为3-66天），每28天5天一次，单独给药时，平均初始剂量为265±73 mg，与放疗联合给药时，平均初始剂量为133±15 mg。8名患者（29.6%）肿瘤体积显著减小（>30%），14名患者（51.9%）肿瘤稳定。在随访的中位时间为29个月（IQR 10-55）后，这22名患者中有8人疾病进展。五名同时接受放疗的患者中，进展无病存活期更长。共有7名患者（25%）死亡（全部因肿瘤进展或治疗并发症），从诊断后77个月（IQR 42-136）和首次替莫唑胺给药后29个月（IQR 16-55）计算。共有18名患者出现不良反应（14例轻度和4例中度或重度）。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医疗治疗药物，但有时会出现肿瘤进展。与放疗联合给药可以增加无进展生存期。版权所有 © 2023 Lamas、Cámara、Fajardo、Remon-Ruiz、Biagetti、Guerrero-Pérez、Araujo-Castro、Mora、Hanzu、Iglesias、García-Centeno和Soto。

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.Copyright © 2023 Lamas, Cámara, Fajardo, Remon-Ruiz, Biagetti, Guerrero-Pérez, Araujo-Castro, Mora, Hanzu, Iglesias, García-Centeno and Soto.