This study focused on patients with type I neurofibromatosis, who currently lack effective drug therapy and have a high recurrence rate after surgical resection. As a MEK inhibitor, Smetinib bisulfate capsule can induce tumor shrinkage by selectively binding mitogen-activated protein kinase (MEK) 1/2 protein, blocking the mitogen-activated protein kinase/extracellular signal regulatory kinase signaling pathway that regulates key cell responses. To create conditions for disease control, radical surgical resection, reducing postoperative recurrence and reducing complications. The purpose of this study was to provide treatment with Smetinib bisulfate for patients with type I neurofibromatosis, observe the therapeutic effect in stages, convert patients without surgical indications into patients with surgical indications, increase the proportion of surgical resection and reduce the recurrence rate. Objective tumor response rate (ORR) after drug treatment was used as the main outcome index in this study. The resectable scope, duration of remission (DOR), progression-free survival (PFS) were used as secondary outcome indicators to investigate the improvement of resectable rate, reduction of resectable scope and postoperative complications, tumor shrinkage effect, and the stability of curative effect of the use of smetinib bisulfate capsule on type I neurofibromatosis.
Neurofibromatosis (NF) has been included in the list of rare diseases in many countries, including China, of which 96% is NF1 subtype, NF1 clinical manifestations are diverse, involve multiple systems, can cause respiratory obstruction, spinal cord compression, motor dysfunction and other serious complications. Plexiform neurofibroma (PN) occurs in 30-50% of patients with NF1. PN progresses rapidly, is associated with severe physical defects, is highly disabling, and is at risk of malignancy. According to the 2023 edition of the Multidisciplinary Guidelines for the Diagnosis and Treatment of type I neurofibromatosis, NF1 patients are more likely than the normal population to develop a variety of benign and malignant tumors, including pNF, CNF, MPNST and OPG. Attention should be paid to the early identification and monitoring of these tumors. The possibility of MPNST should be highly vigilant for neurofibromas with growth acceleration, pain, and texture hardening. At the same time, systemic evaluation should be performed, and early surgery should be performed as far as possible for patients without signs of distant metastasis, while radiotherapy, chemotherapy and targeted therapy can be selected for patients with distant metastasis. neurofibromatosis type 1 (NF1) is an autosomal dominant disorder in which 50% of patients have familial inherited mutations and 50% have sporadic mutations. NF1 gene encodes neurofibrin, down-regulates the activity of Ras-Raf pathway, and inhibits cell proliferation. Neurofibrin deficiency can lead to overactivation of RAS pathway, resulting in uncontrolled cell proliferation in patients with NF1 \[5\]. At present, surgery is the most commonly used and most important treatment for neurofibromatosis, and neurofibroma has the characteristic of growing along the nerve root, so it is difficult to solve all the lesions through surgery. The lesions consist of a wide range of nerve and vascular tissues mixed with normal tissues, and the surgical resection is difficult and bleeding is frequent, and the recurrence after incomplete resection is as high as 50%. As a MEK inhibitor, Smetinib bisulfate capsule can induce tumor shrinkage by selectively binding mitogen-activated protein kinase (MEK) 1/2 protein to block the mitogen-activated protein kinase/extracellular signal regulatory kinase signaling pathway that regulates key cellular responses. To create conditions for disease control, radical surgical resection, reducing postoperative recurrence and reducing complications. Based on the targeted therapy of Smetinib bisulfate capsule, this study administered medication to enrolled patients. By monitoring the tumor shrinkage effect of patients with solid tumors and evaluating postoperative surgical indications for patients without surgical indications before medication, the effectiveness of smetinib bisulfate capsule in the treatment of NF1 was verified.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Patients without indications for surgical excision were evaluated with 6 cycles of daily oral smetinib capsules (20-50mg bid) for 30 days, individually calculated based on patient body surface area (BSA)
Objective response rate (ORR)
Percentage of patients with a partial response confirmed by analysis after 6 cycles of drug therapy. A partial response is defined as a reduction in the target neurofibroma volume of ≥ 20% from baseline. A confirmed partial response was defined as a partial response assessed by successive re-staging examinations at intervals of ≥ 3 months.
Time frame: Within two years of medication
The scope of the operation can be resected
On the premise of not damaging the important organs and nerve functions that the tumor has invaded, according to the proportion of tumor resection, it can be divided into total resection/near-total resection (resection range ≥ 90%), subtotal resection (90% \> resection range ≥ 50%), and partial resection (resection range \< 50%).
Time frame: Within two years of medication
Duration of response (DOR)
Refers to the time from the first evaluation of a tumor as CR or PR to the first evaluation as PD or death from any cause.
Time frame: Within two years of medication
Progression-free survival (PFS)
Refers to the time from the start of treatment in the trial until tumor progression or death from any cause, whichever occurs first.
Time frame: Within two years of medication
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.