Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors

Author:

Shatara Margaret1ORCID,Blue Megan2,Stanek Joseph2ORCID,Liu Yin A3,Prevedello Daniel M4,Giglio Pierre5ORCID,Puduvalli Vinay K6ORCID,Gardner Sharon L7,Allen Jeffrey C7,Wong Kenneth K89,Nelson Marvin D10,Gilles Floyd H11,Adams Roberta H12,Pauly Jasmine13,O’Halloran Katrina8,Margol Ashley S8,Dhall Girish14ORCID,Finlay Jonathan L2

Affiliation:

1. Division of Hematology and Oncology, St. Louis Children’s Hospital, Washington University School of Medicine , St. Louis, Missouri , USA

2. Division of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children’s Hospital and Ohio State University College of Medicine , Columbus, Ohio , USA

3. Departments of Ophthalmology, Neurology, and Neurosurgery, University of California, Davis , Sacramento, California , USA

4. Department of Neurological Surgery, Ohio State University Wexner Medical Center , Columbus, Ohio , USA

5. Division of Neuro-Oncology, Ohio State University Wexner Medical Center, James Cancer Center , Columbus, Ohio , USA

6. Department of Neuro-oncology, MD Anderson Cancer Center , Houston, Texas , USA

7. Department of Pediatrics, New York University Grossman School of Medicine , New York, New York , USA

8. Division of Hematology and Oncology, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles and Keck School of Medicine of University of Southern California , Los Angeles, California , USA

9. Department of Radiation Oncology, University of Southern California , Los Angeles, California , USA

10. Department of Radiology, Children’s Hospital of Los Angeles , Los Angeles, California , USA

11. Department of Pathology, Children’s Hospital of Los Angeles , Los Angeles, California , USA

12. Phoenix Children’s Center for Cancer & Blood Disorders, University of Arizona School of Medicine—Phoenix, and Mayo Clinic , Arizona , USA

13. Division of Hematology and Oncology, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles , California , USA

14. Division of Pediatric Hematology/Oncology, Children’s Hospital of Alabama and the University of Alabama at Birmingham , Birmingham, Alabama , USA

Abstract

AbstractBackgroundPatients 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).MethodsA 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.ResultsA 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.ConclusionsGemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

Funder

The NEXT Consortium

“The Childhood Brain Tumor Foundation”

“Making Headway Foundation”

Publisher

Oxford University Press (OUP)

Subject

Medicine (miscellaneous)

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