II期NEXT/CNS-GCT-4试验的最终报告：GemPOx方案序贯清髓性化疗用于复发性颅内生殖细胞肿瘤
Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors.
作者信息
Shatara Margaret, Blue Megan, Stanek Joseph, Liu Yin A, Prevedello Daniel M, Giglio Pierre, Puduvalli Vinay K, Gardner Sharon L, Allen Jeffrey C, Wong Kenneth K, Nelson Marvin D, Gilles Floyd H, Adams Roberta H, Pauly Jasmine, O'Halloran Katrina, Margol Ashley S, Dhall Girish, Finlay Jonathan L
机构信息
Division of Hematology and Oncology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri, USA.
Division of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus, Ohio, USA.
出版信息
Neurooncol Pract. 2023 Oct 14;11(2):188-198. doi: 10.1093/nop/npad067. eCollection 2024 Apr.
BACKGROUND
Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction 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 germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).
METHODS
A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 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
A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 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.
CONCLUSIONS
GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.
背景
复发性颅内生殖细胞瘤患者可通过标准化疗方案和/或再次放疗实现持久缓解；然而，复发性和/或难治性颅内非生殖细胞性生殖细胞肿瘤（NGGCTs）患者因其预后较差，需要创新疗法。据报道，采用再诱导化疗以达到最小残留疾病，随后进行含自体造血祖细胞救援（AuHPCR）的清髓性化疗（HDCx）可改善预后。我们进行了一项II期试验，评估为复发性颅内生殖细胞肿瘤开发的由吉西他滨、紫杉醇和奥沙利铂组成的三联药物组合（GemPOx）的疗效和毒性。
方法
共有9例确诊为复发性或难治性颅内生殖细胞肿瘤的患者在签署知情同意书后入组，接受至少2个周期的GemPOx治疗，其中除1例患者外均为复发性或难治性NGGCTs。1例疾病进展的患者经病理证实已恶变为纯胚胎性横纹肌肉瘤（无生殖细胞肿瘤成分），因此不符合条件，未纳入分析。获得足够缓解的患者继续接受含AuHPCR的HDCx治疗。根据影像学肿瘤评估和肿瘤标志物确定治疗反应。
结果
共有7例患者获得足够缓解并继续接受HDCx和AuHPCR治疗，其中5例随后接受了额外的放疗。共有2例患者在接受GemPOx治疗时出现疾病进展。骨髓抑制和转氨酶升高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NGGCTs，1例生殖细胞瘤）存活，无疾病证据。
结论
GemPOx在促进干细胞动员方面显示出疗效，从而提高了HDCx和放疗的可行性。
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