Sunitinib Malate plus Lomustine for Patients with Temozolomide-refractory Recurrent Anaplastic or Low-grade Glioma

Area of Science:

• Neuro-Oncology
• Cancer Therapeutics
• Molecular Targeted Therapy

Background:

• Tyrosine kinase signaling via VEGFR2, PDGFR-α, and KIT is crucial for glioma angiogenesis and survival.
• Recurrent anaplastic and low-grade gliomas often become refractory to temozolomide treatment.
• Targeting these receptor tyrosine kinases presents a potential therapeutic strategy.

Purpose of the Study:

• To evaluate the efficacy and safety of sunitinib malate in combination with lomustine.
• To assess the treatment in patients with temozolomide-refractory recurrent anaplastic or low-grade glioma.

Main Methods:

• A clinical trial involving thirteen patients with temozolomide-refractory recurrent anaplastic or low-grade glioma.
• Patients received sunitinib malate, a multi-targeted tyrosine kinase inhibitor, combined with lomustine.
• Tumor response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria.

Main Results:

• The combination regimen was generally well-tolerated, with frequent Grade 3/4 adverse events including fatigue, thrombocytopenia, neutropenia, and lymphopenia.
• Objective tumor responses included one complete response, one unconfirmed partial response, and three cases of stable disease.
• Median progression-free survival was 1.8 months, and median overall survival was 6.7 months.

Conclusions:

• The combination of sunitinib malate and lomustine demonstrated limited anti-tumor activity in this patient cohort.
• The regimen was well-tolerated but not sufficiently active to justify further investigation in unselected patients with temozolomide-refractory glioma.