Sirolimus Improves Pain in NF1 Patients With Severe Plexiform Neurofibromas

被引:26
|
作者
Hua, Camille [1 ]
Zehou, Ouidad [1 ]
Ducassou, Stephane [2 ]
Minard-Colin, Veronique [3 ]
Hamel-Teillac, Dominique [4 ]
Wolkenstein, Pierre [1 ,5 ]
Valeyrie-Allanore, Laurence [1 ,5 ]
机构
[1] Hop Henri Mondor, AP HP, Ctr Reference Neurofibromatoses, Serv Dermatol, F-94010 Creteil, France
[2] CHU Bordeaux, GH Pellegrin, Serv Onco Hematol Pediat, Bordeaux, France
[3] Inst Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France
[4] Hop Prive Antony, Serv Dermatol Pediat, Antony, France
[5] Univ Paris Est, Hop Henri Mondor, AP HP, LIC EA 4393, Creteil, France
关键词
neurofibromatosis type 1; plexiform neurofibromas; therapeutics; pain management; sirolimus; NERVE SHEATH TUMORS; MAMMALIAN TARGET; TYPE-1; NEUROFIBROMATOSIS; RAPAMYCIN PATHWAY; LOCAL TRANSLATION; SCHWANN-CELLS; RAS PROTEINS; IN-VIVO; MTOR; INFLAMMATION;
D O I
10.1542/peds.2013-1224
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Plexiform neurofibromas (PNs) are common and potentially debilitating complications of neurofibromatosis 1 (NF1). These benign nerve-sheath tumors are associated with significant pain and morbidity because they compress vital structures. The mammalian target of rapamycin (mTOR) pathway is a major mediator involved in tumor growth in NF1. We present 3 cases of patients with NF1, aged 8, 16, and 17 years, followed for inoperable and symptomatic PNs; patients received sirolimus for life-threatening and painful neurofibromas after multidisciplinary consultation. Epidemiologic, clinical, and radiologic data were retrospectively collected. The volume of PNs did not differ between baseline and 12-month follow-up and pain was alleviated, with withdrawal of analgesics in 2 cases at 6 months, and significantly decreased for the third case. Sirolimus for inoperable symptomatic PNs in patients with NF1 permitted stabilization of mass and produced unpredictable and important alleviation of pain in all cases with good tolerance. This treatment was proposed in extreme cases, in absence of therapeutic alternatives, after multidisciplinary consensus. The mTOR pathway may be both a major mediator of NF1 tumor growth and regulator of nociceptor sensitivity. mTOR inhibitors clinically used as anticancer and immunosuppressant drugs could be a potential treatment of chronic pain.
引用
收藏
页码:E1792 / E1797
页数:6
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