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Preradiation Chemotherapy for Adult High-risk Medulloblastoma: A Trial of the ECOG-ACRIN Cancer Research Group (E4397)

Moots, Paul, L., MD*; O’Neill, Anne, MS; Londer, Harold, MD; Mehta, Minesh, MD§; Blumenthal, Deborah, T., MD; Barger, Geoffrey, R., MD; Grunnet, Margaret, L., MD#; Grossman, Stuart, MD**; Gilbert, Mark, R., MD††; Schiff, David, MD‡‡

American Journal of Clinical Oncology: June 2018 - Volume 41 - Issue 6 - p 588–594
doi: 10.1097/COC.0000000000000326
Original Articles: Central Nervous System

Objectives: To assess the long-term outcomes and objective response (OR) to preradiation chemotherapy and radiation in adult high-risk medulloblastoma.

Materials and Methods: In this prospective phase II trial, adults with high-risk medulloblastoma were treated with 3 cycles of preradiation cisplatin, etoposide, cyclophosphamide, and vincristine followed by craniospinal radiation (CSI). OR, progression-free survival (PFS), overall survival (OS), and toxicities were assessed.

Results: Eleven patients were enrolled over a 6-year period. Six (55%) had subarachnoid metastases. Two (18%) had an OR to preradiation chemotherapy. Two (18%) progressed while on chemotherapy. Completion of CSI was not compromised. The OR rate after chemotherapy and radiation was 45% (5/11). Nonevaluable patients at both time-points weakened the response data conclusions. Median PFS was 43.8 months. Five-year PFS was 27%. Five-year OS was 55%. Nonmetastatic (M0) and metastatic (M+) patients had similar outcomes.

Conclusions: The OR to this preradiation chemotherapy regimen is lower than anticipated from the adult and pediatric literature raising a question about comparative efficacy of chemotherapy in different age groups. The OS achieved is similar to retrospective adult series, but worse than pediatric outcomes. Although this regimen can be administered without compromising delivery of CSI, our results do not provide support for the use of this neoadjuvant chemotherapy for adult medulloblastoma.

*Vanderbilt University and TVHS, Nashville, TN

Dana Farber Cancer Institute, Boston, MA

Humphrey Cancer Center, Robbinsdale, MN

§Department of Human Oncology, University of Wisconsin, Madison, WI

Division of Oncology, University of Utah, Salt Lake City, UT

Department of Neurology, Wayne State University, Detroit, MI

#University of Connecticut Health Center, Farmington, CT

**Johns Hopkins University Medical Center, Baltimore, MD

††M.D. Anderson Cancer Center, Houston, TX

‡‡University of Virginia Medical Center, Charlottesville, VA

Present address: Minesh Mehta, MD, University of Maryland, Baltimore, MD.

Present address: Deborah T. Blumenthal, MD, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.

Present address: Mark R. Gilbert, MD, National Institutes of Health, Bethesda, MD.

This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA180820, CA180794, CA21115, CA23318, CA66636, CA180847, CA49957, CA189863, CA35267, CA180799, CA21076, CA180888, CA32102, CA180818, CA58861, CA180835, CA14028, CA180802, CA16116, CA180844, CA39229, CA180858, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

M.M. has served in the past as a consultant for Genentech, Novartis, with stock options in Pharmacyclics, and is on the Board of Directors of Pharmacyclics. The remaining authors declare no conflicts of interest.

Reprints: Paul L. Moots, MD, Vanderbilt University and TVHS, Nashville, TN 37232. E-mail: paul.moots@vanderbilt.edu.

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