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

Publication Date

4-1-2024

Journal

Neuro-Oncology Practice

DOI

10.1093/nop/npad067

PMID

38496907

PMCID

PMC10940828

PubMedCentral® Posted Date

10-14-2023

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

GemPOx, long-term survival, objective response rate, outcomes, relapsed intracranial GCTs

Published Open-Access

yes

Recommended Citation

Shatara, Margaret; Blue, Megan; Stanek, Joseph; et al., "Final Report of the Phase II NEXT/CNS-GCT-4 Trial: GemPOx Followed by Marrow-Ablative Chemotherapy for Recurrent Intracranial Germ Cell Tumors" (2024). Faculty, Staff and Student Publications. 3827.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3827