Li Kun Chen

Gefitinib alone or with concomitant whole brain radiotherapy for patients with brain metastasis from non-small-cell lung cancer: A retrospective study

BACKGROUND Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. METHODS We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250 mg/day, gefitinib group) or with concomitant WBRT (40 Gy/20 f/4 w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. RESULTS The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease control rate of BM was 71.1% in gefitinib- WBRT group and 42.2% in gefitinib group (P=0.006). The median time to progression of BM was 10.6 months in gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median overall survival (OS) of gefitinib-WBRT and gefitinib alone group was 23.40 months and 14.83 months, respectively (HR, 0.432, P=0.002). CONCLUSION Gefitinib plus concomitant WBRT had higher response rate of BM and significant improvement in OS compared with gefitinib alone in treatment of BM from NSCLC.

Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer.

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%–95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

Changes of bone resorption marker (NTX) in chemotherapy plus zoledronic acid versus chemotherapy alone for nasopharyngeal cancer patients with bone metastases

BACKGROUND Zoledronic acid (ZOL) is the only bisphosphonate with demonstrated efficacy for the prevention of skeletal-related events (SRE) in patients with bone metastases of diverse malignant tumours. A recent large, retrospective analysis reported that a reduction in N-telopeptide of type I collagen (NTX) provided a continuum of reduced SRE risk and survival benefit in patients with bone metastases. The present prospective, open-label, randomised, phase II trial sought to evaluate NTX changes after ZOL administration in nasopharyngeal cancer (NPC) patients with bone metastases (BM). METHODS Newly diagnosed NPC patients (n = 60) with bone metastasis were randomised to the test group (n = 30), who received chemotherapy with cisplatin plus 5-fluorouracil (5-FU) (q3wks) and intravenous ZOL (4 mg, q4 wks) for 3 months, or a control group (n = 30), who received cisplatin plus 5-FU alone. Urinary NTX was measured by ELISA at baseline and 1, 2 and 3months after administration of ZOL. RESULTS The median baseline NTX level was no different in both the test and control patients (75.4 and 94.6 nM bone collagen equivalent units/mM creatinine, respectively; p = 0.370). NTX decreased by 61.5% within 1month in the test group, but only by 6.6% in the control group (p < 0.01). After 3 months, the test group reached a maximum reduction (-85.9%) as compared to the other time points and to the control group (-51.5%) (p = 0.001). More patients in the test group achieved normal NTX than that in the control group (p=0.042). CONCLUSIONS ZOL administered with chemotherapy immediately and consistently reduced NTX levels for NPC patients with bone metastasis. Larger prospective randomised trial to confirm the efficacy of ZOL in NPC patients with bone metastases is pending.

New phase transition associated with configuration of oxygen vacancies in VO1.965 nanometer ceramics

Little attention was paid to the effect of oxygen vacancy configuration, although it is well known that oxygen vacancy plays a key role in determining the electrical and optical properties of VO2. By means of different heat treatments, the oxygen vacancy configuration in VO1.965 nanometer ceramic is controlled and its behavior is investigated in detail. It is found that VO1.965 ceramic aged at 60°C for a day displays a new first order phase transformation at about 30°C, which is associated with the oxygen vacancy distribution. An explanation based on the symmetry conforming principle is tentatively presented.

Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non–Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center

Micro‐Abstract Current prognosis models for brain metastases (BMs) have not addressed the issue of either newly diagnosed non–small‐cell lung cancer with BMs or the lung cancer genotype. Using the data from 1158 patients, we built a new prognosis model for initially diagnosed non–small‐cell lung cancer with BMs. Our model includes the epidermal growth factor receptor genotype as an important prognostic factor for the first time and shows superiority for predicting patient prognosis. Background: The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non–small‐cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). Patients and Methods: The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat‐Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. Results: We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR‐tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low‐ (score, 0‐2), moderate‐ (score, 3‐5), and high‐risk (score 6‐7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. Conclusion: Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs.

Long-lasting response to third-line crizotinib treatment in a patient with non-small cell lung cancer with brain metastases and poor performance status

Identification of the anaplastic lymphoma kinase (ALK) gene has refined the classification of non‐small cell lung cancer (NSCLC) and promoted research on molecularly targeted drugs such as crizotinib, an ALK inhibitor with good efficacy, in ALK‐rearranged NSCLC. At present, few studies have reported the efficacy of crizotinib in patients with ALK‐rearranged NSCLC with brain metastases. In a patient with NSCLC harboring ALK‐rearrangement who had brain metastases and poor performance status (PS), we obtained a durable response with crizotinib administered following multi‐line chemotherapy regimens.

Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study.

Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC). However, the efficacy of consolidation chemotherapy (CCT) in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC) who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results Among the 177 patients, 72 (41%) received CCT and 105 (59%) did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031), whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118). The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035), having undergone prophylactic cranial irradiation (P<0.001), and having received CCT (P=0.002) could serve as favorable independent prognostic factors for PFS. Multivariate analysis for OS also showed that having undergone PCI (P<0.001) and having received CCT (P=0.006) were independent significant prognostic factors. Conclusion CCT can improve PFS for patients with stage IIIA and IIIB SCLC following CCRT without significantly increasing treatment-related toxicities.

Phase I dose-escalation study of aflibercept plus docetaxel in nasopharyngeal carcinoma and other solid tumors

AIM To confirm whether the aflibercept dose, plus docetaxel, in western study TCD6120 is appropriate for Chinese patients with nasopharyngeal carcinoma (NPC) and other solid tumors. MATERIALS & METHODS To assess dose-limiting toxicity of every 3-week 4 mg/kg or 6 mg/kg aflibercept plus 75 mg/m(2) docetaxel. RESULTS Previously treated patients (16 with NPC and 4 with lung cancer) were enrolled. At 6 mg/kg aflibercept: one dose-limiting toxicity was seen (neutropenic infection); the most frequently reported all-grade adverse events were oropharyngeal pain, stomatitis and alopecia; the most frequently reported grade 3/4 adverse events were oropharyngeal pain, stomatitis and neutropenic infection. Eleven patients had partial response and 3 had stable disease. CONCLUSION Preliminary efficacy data for docetaxel/aflibercept are encouraging in Chinese patients with NPC. TRIAL REGISTRATION This study was registered with the University Hospital Medical Information Network Clinical Trials Registry ( ClinicalTrials.gov , NCT01148615).