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替莫唑胺治疗脑胶质瘤 1 年耐受性差:国家神经肿瘤中心的真实世界经验。

One year of procarbazine lomustine and vincristine is poorly tolerated in low grade glioma: a real world experience in a national neuro-oncology centre.

机构信息

Department of Medical Oncology, Beaumont Hospital, Dublin 9, Ireland.

Cancer Clinical Trials and Research Unit, Beaumont Hospital, Dublin 9, Ireland.

出版信息

BMC Cancer. 2021 Feb 8;21(1):140. doi: 10.1186/s12885-021-07809-5.

Abstract

BACKGROUND

Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice.

METHODS

We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities.

RESULTS

Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia.

CONCLUSION

Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.

摘要

背景

在接受最佳局部治疗后,洛莫司汀、丙卡巴肼和长春新碱(PCV)辅助治疗可改善低级别胶质瘤(LGG)患者的总生存期(OS)。然而,PCV 治疗 1 年与显著的毒性相关。在关键性 RTOG 9802 随机对照试验中,大约一半的患者在 6 个月后停止治疗。由于临床试验中的患者可能更健康,我们旨在进一步探索 PCV 化疗在常规临床实践中的耐受性。

方法

我们在国家神经肿瘤中心进行了一项回顾性研究,时间为 2014 年至 2018 年。在此期间接受 PCV 治疗的患者被纳入研究。主要目的是评估治疗的耐受性。次要目标包括评估治疗延迟、剂量调整和毒性。

结果

共有 41 例患者纳入研究,24 例(58%)为男性,21 例(51%)年龄≥40 岁。38 例(93%)患者接受了手术切除,所有患者在化疗前均接受了辅助放疗。完成的环数中位数分别为:丙卡巴肼 3 个,洛莫司汀 2 个,长春新碱 4 个。仅有 4 例(10%)患者未进行剂量调整,完成了全部 6 个周期的 PCV 治疗。随着化疗周期的进展,剂量强度普遍下降。第 1 周期与第 6 周期的剂量强度分别为:丙卡巴肼(98%对 46%)、洛莫司汀(94%对 48%)和长春新碱(93%对 50%)。血液学毒性很常见。6 例(14%)患者发生 3 级-4 级血小板减少症,13 例(31%)患者发生 3 级-4 级中性粒细胞减少症。

结论

PCV 方案在临床实践中常观察到毒性。为了提高耐受性,可能最好从化疗开始就调整剂量,或考虑替代化疗,特别是在年龄较大的 LGG 患者中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d71/7869199/fd0a4f1ce285/12885_2021_7809_Fig1_HTML.jpg

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