SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors
Christine S. Higham,
Seth M. Steinberg,
Eva Dombi,
Arie Perry,
Lee J. Helman,
Scott M. Schuetze,
Joseph A. Ludwig,
Arthur Staddon,
Mohammed M. Milhem,
Daniel Rushing,
Robin L. Jones,
Michael Livingston,
Stewart Goldman,
Christopher Moertel,
Lars Wagner,
David Janhofer,
Christina M. Annunziata,
Denise Reinke,
Lauren Long,
David Viskochil,
Larry Baker,
Brigitte C. Widemann
Affiliations
Christine S. Higham
Pediatric Oncology Branch, NCI, CCR, Bethesda, MD, USA
Seth M. Steinberg
Biostatistics and Data Management Section, NCI, Bethesda, MD, USA
Eva Dombi
Pediatric Oncology Branch, NCI, CCR, Bethesda, MD, USA
Arie Perry
University of California, San Francisco, San Francisco, CA, USA
Lee J. Helman
Pediatric Oncology Branch, NCI, CCR, Bethesda, MD, USA
Scott M. Schuetze
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
Joseph A. Ludwig
MD Anderson Cancer Center, Houston, TX, USA
Arthur Staddon
University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA, USA
Mohammed M. Milhem
University of Iowa Hospital and Clinics, Iowa City, IA, USA
Daniel Rushing
Indiana University, Indianapolis, IN, USA
Robin L. Jones
University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Michael Livingston
Levine Cancer Center, Charlotte, NC, USA
Stewart Goldman
Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA
Christopher Moertel
University of Minnesota Masonic Children’s Hospital, Minneapolis, MN, USA
Lars Wagner
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
David Janhofer
Pediatric Oncology Branch, NCI, CCR, Bethesda, MD, USA
Christina M. Annunziata
Women’s Malignancies Branch, NCI, Bethesda, MD, USA
Denise Reinke
SARC, Ann Arbor, MI, USA
Lauren Long
Pediatric Oncology Branch, NCI, CCR, Bethesda, MD, USA
David Viskochil
University of Utah, Salt Lake City, UT, USA
Larry Baker
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
Brigitte C. Widemann
Pediatric Oncology Branch, NCI, CCR, Bethesda, MD, USA
Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.
