Final Report of the Phase II NEXT/CNS-GCT-4 Trial: GemPOx followed by Marrow-ablative Chemotherapy for Recurrent Intracranial Germ Cell Tumors

IF 2.4 Q2 CLINICAL NEUROLOGY

Neuro-oncology practice Pub Date : 2023-10-14 DOI:10.1093/nop/npad067

Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O’Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

{"title":"Final Report of the Phase II NEXT/CNS-GCT-4 Trial: GemPOx followed by Marrow-ablative Chemotherapy for Recurrent Intracranial Germ Cell Tumors","authors":"Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O’Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay","doi":"10.1093/nop/npad067","DOIUrl":null,"url":null,"abstract":"Abstract Background Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or re-irradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial non-germinomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using re-induction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial GCTs (iGCTs) consisting of gemcitabine, paclitaxel and oxaliplatin (GemPOx). Methods Nine patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least two cycles of GemPOx, of which all but one had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results Seven patients achieved sufficient response and proceeded with HDCx and AuHPCR, and five subsequently received additional radiotherapy. Two patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusion GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.","PeriodicalId":19234,"journal":{"name":"Neuro-oncology practice","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology practice","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/nop/npad067","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Abstract Background Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or re-irradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial non-germinomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using re-induction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial GCTs (iGCTs) consisting of gemcitabine, paclitaxel and oxaliplatin (GemPOx). Methods Nine patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least two cycles of GemPOx, of which all but one had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results Seven patients achieved sufficient response and proceeded with HDCx and AuHPCR, and five subsequently received additional radiotherapy. Two patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusion GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

查看原文本刊更多论文

II期NEXT/CNS-GCT-4试验的最终报告:GemPOx后骨髓消融化疗治疗复发性颅内生殖细胞瘤

背景复发的颅内生殖细胞瘤患者可以通过标准化疗方案和/或再照射获得持久缓解;然而，由于复发和/或难治性颅内非生发性生殖细胞肿瘤(NGGCTs)预后不良，需要创新的治疗方法。有报道称，使用再诱导化疗来实现最小残留疾病，然后再使用骨髓消融化疗(HDCx)和自体造血祖细胞拯救(AuHPCR)来改善预后。我们进行了一项II期试验，评估由吉西他滨、紫杉醇和奥沙利铂(GemPOx)组成的三药联合治疗复发性颅内gct (igct)的疗效和毒性。方法入选9例确认为复发或难治性颅内GCT的患者，在签署知情同意书后，接受至少2个疗程的GemPOx治疗，其中除1例外均为复发或难治性nggct。1例进展性疾病患者病理证实恶性转化为纯胚胎性横纹肌肉瘤(无GCT元素)，因此不符合条件，未纳入分析。有足够反应的患者继续接受AuHPCR的HDCx治疗。治疗效果是根据放射学肿瘤评估和肿瘤标志物来确定的。结果7例患者获得充分缓解，并进行了HDCx和AuHPCR治疗，5例患者随后接受了额外的放疗。两名患者在接受天花治疗时病情进展。骨髓抑制和转氨炎是最常见的治疗相关不良事件。平均随访44个月，4例患者(3例nggct, 1例生殖细胞瘤)存活，无疾病证据。结论GemPOx具有促进干细胞动员的作用，促进了HDCx和放疗的可行性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuro-oncology practice CLINICAL NEUROLOGY-

CiteScore

5.30

自引率

11.10%

发文量

期刊介绍： Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving