Medications for Neurofibromatosis Type 1
Selumetinib is the only FDA-approved medication for NF1, specifically indicated for children aged 2 years and older with symptomatic, inoperable plexiform neurofibromas, producing clinically meaningful tumor shrinkage and functional improvement. 1
Targeted Therapy for Plexiform Neurofibromas
MEK Inhibitors (Primary Treatment)
Selumetinib produces tumor volume reductions ≥20% in approximately 70% of patients after more than 4 years of treatment, with responses lasting beyond 1 year in most cases. 1, 2
Pain reduction is significant and occurs early, with tumor pain intensity dropping from an average score of 2.2 to 0.6 within 12 months and remaining low at 0.58 over 4 years. 2
Trametinib serves as an alternative MEK inhibitor when selumetinib is unavailable, with demonstrated efficacy in plexiform neurofibromas. 1
Cabozantinib (receptor tyrosine kinase inhibitor) has shown activity in patients aged 16 years and older with NF1 plexiform neurofibromas. 3
Indications for MEK Inhibitor Therapy
- Visual decline or risk to vision from plexiform neurofibromas 1
- Progressive tumor growth 1
- New or worsening functional deficits 1
- Progressive disfigurement 1
Important Caveat
It remains unknown whether MEK inhibitors modify the risk of transformation to atypical neurofibromatous neoplasm of uncertain biological potential (ANNUBP) or malignant peripheral nerve sheath tumor (MPNST), mandating close clinical monitoring throughout treatment. 3
Symptomatic Management
Pain Management
Chronic pain in NF1 adults is common (mean severity 6.6/10) and requires a multimodal approach combining pharmacologic and non-pharmacologic strategies. 4
Medication, physical therapy, transcutaneous electrical nerve stimulation (TENS), and surgery for compressive tumors are recommended for NF1-related neuropathy and pain. 4
Screening with pain-interference scales should be implemented routinely, with referral to pain clinics employing both pharmacologic and non-pharmacologic approaches. 3, 4
Glomus tumors causing fingertip pain are surgically curable, making early identification critical. 4
Neurological Symptoms
NF1-associated migraine, seizures, and sleep disorders should be treated with standard medications used in the non-NF1 population. 3
Malignant Peripheral Nerve Sheath Tumor (MPNST)
Chemotherapy for Advanced Disease
In advanced and metastatic MPNST, doxorubicin plus ifosfamide produces response rates of approximately 21% in multi-institutional retrospective studies. 3, 5
Surgery remains the cornerstone of treatment for high-grade MPNST, with the aim of achieving clear margins, demonstrating benefit even for large abdominal tumors. 3, 5
Adjuvant chemotherapy and radiation may have a role in some non-metastatic MPNST patients, though randomized studies are lacking. 3
Medications to Avoid or Use with Caution
Hormonal Contraceptives
Oral estrogen-progestogen or pure progestogen preparations appear safe, with 89% of women reporting no associated neurofibroma growth. 3
High-dose depot contraceptives containing synthetic progesterone should be avoided, as 3% of women reported significant tumor growth with these formulations. 3
Critical Clinical Monitoring
New-onset or increasingly severe pain must be evaluated immediately as a possible symptom of MPNST, which requires urgent imaging and potential biopsy. 4, 5
The risk of NF1-associated MPNST increases with age: 8.5% by age 30,12.3% by age 50, and 15.8% by age 85, necessitating lifelong vigilance. 5