Pilot study of radiofrequency hyperthermia in combination with gefitinib in gefitinib‐effective patients with advanced NSCLC

Abstract

BackgroundNon‐small‐cell lung cancer (NSCLC) is the leading cause of death from cancer in China. Gefitinib is effective for patients with positive epidermal growth factor receptor gene mutation; however, acquired drug resistance counteracts the duration response. Hyperthermia is widely clinically applied in the treatment of solid tumors. This pilot study was designed to evaluate the feasibility of the combination of gefitinib and hyperthermia.MethodsPatients newly diagnosed with advanced NSCLC were screened. Eleven patients who responded to first‐line gefitinib treatment were enrolled in the study. Along with 250 mg gefitinib daily, local radiofrequency hyperthermia was administered twice a week until tumor progression was observed. The serum, heat shock protein (HSP)70, was also frequently detected during the course.ResultsThe most common toxicity included skin rash (81.8%) and abnormal liver function (45.5%) when treated with gefitinib, and fatty scleroma (36.4%) was observed when combined with hyperthermia. Grade 3 side effects (skin rash) occurred in only one patient. Median progression‐free survival was 22 months (95% confidence interval [CI]: 12.95–31.05 months) and median overall survival was 26 months (95% CI: 22.81–29.19 months). Serum HSP70 concentration increased and maintained a significantly high level compared with the baseline before hyperthermia administration.ConclusionsThe novel therapy of gefitinib combined with radiofrequency hyperthermia is safe and effective for advanced NSCLC patients. Whether an improvement in therapeutic efficacy is associated with the elevation of serum HSP70 concentration requires further study.

Retracted: Effects of ebv‐miR‐BART7 on tumorigenicity, metastasis, and TRAIL sensitivity of non‐small cell lung cancer

“…2 In China, NSCLC is the leading cause responsible for the death of patients with malignant tumor, with only 10% 5-year survival rate. 3 Despite surgery as the mainstay of treatment for NSCLC patients at an early stage, approximately 80% of patients are more likely to be in the advanced stage when diagnosed 4 Recently, chemotherapy is one of the main treatments, but the drug resistance rate is still higher in advanced NSCLC patients. 5 TNF-related apoptosis-inducing ligand (TRAIL), also known as Apoptosisin 2 Ligand (Apo2L), is a member of the tumor necrosis factor superfamily, which could induce apoptosis by binding to the death receptors, TRAIL-R1(DR4) and TRAIL-R2 (DR5).…”

Microwave ablation combined with EGFR-TKIs versus only EGFR-TKIs in advanced NSCLC patients with EGFR-sensitive mutations

“…[ 19 , 20 ] For those with brain progression, SBRT or SRT was the first choice, and the EGFR-TKIs were continued. [ 20 – 22 ] For patients with local disease progression, local treatments including radiation or thermal ablation in combination with previous EGFR-TKIs were recommended [ 20 , 23 , 24 , 33 – 35 ]. However, chemotherapy and transfer to a third EGFR-TKI were treatment options for those with widespread metastasis.…”

“…The median OS, PFS after RT, and OS after RT were 50 months, 15 months, and 18 months, respectively. Qin et al [ 35 ] reported that when patients who responded to EGFR-TKIs received EGFR-TKIs and local radiofrequency hyperthermia, the PFS and OS were 22 months and 26 months, respectively. The difference in PFS indicated that local treatments, which did not focus on all tumor sites, did not have a survival advantage for patients with EGFR-sensitive mutations treated with MWA plus EGFR-TKIs.…”

Novel Drugs with High Efficacy against Tumor Angiogenesis

“…Elevated levels of HSP have been detected in many solid tumors, including non-small cell lung cancer, esophageal cancer, and lymphoma. [125][126][127]. HSPs are highly conserved molecular chaperone proteins originally thought to be stressresponsive proteins required for the survival of cells or organisms after exposure to heat stress [128].…”