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

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.