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Sirolimus for non‐progressive NF1‐associated plexiform neurofibromas: An NF clinical trials consortium phase II study
Author(s) -
Weiss Brian,
Widemann Brigitte C.,
Wolters Pamela,
Dombi Eva,
Vinks Alexander A.,
Cantor Alan,
Korf Bruce,
Perentesis John,
Gutmann David H.,
Schorry Elizabeth,
Packer Roger,
Fisher Michael J.
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24873
Subject(s) - medicine , sirolimus , neurofibromatosis , pi3k/akt/mtor pathway , clinical trial , quality of life (healthcare) , oncology , pathology , signal transduction , biochemistry , chemistry , nursing
Background Patients with Neurofibromatosis Type 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. There are no standard treatment options for PN other than surgery, which is often difficult due to the extensive growth and invasion of surrounding tissues. Mammalian Target of Rapamcyin (mTOR) acts as a master switch of cellular catabolism and anabolism and controls protein translation, angiogenesis, cell motility, and proliferation. The NF1 tumor suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a macrolide antibiotic that inhibits mTOR activity. Procedure We conducted a 2‐stratum phase II clinical trial. In stratum 2, we sought to determine whether the mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic responses in inoperable PNs in the absence of documented radiographic progression at trial entry. Results No subjects had better than stable disease by the end of six courses. However, the children's self‐report responses on health‐related quality of life questionnaires indicated a significant improvement in the mean scores of the Emotional and School domains from baseline to 6 months of sirolimus. Conclusions This study efficiently documented that sirolimus does not cause shrinkage of non‐progressive PNs, and thus should not be considered as a treatment option for these tumors. This study also supports the inclusion of patient‐reported outcome measures in clinical trials to assess areas of benefit that are not addressed by the medical outcomes. Pediatr Blood Cancer 2014;61:982–986. © 2013 Wiley Periodicals, Inc.