Microwave ablation plus chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a multicenter, randomized, controlled, phase III clinical trial.

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

The correlation of bone morphogenetic protein 2 with poor prognosis in glioma patients.

Glioma is the most common type of human intracranial cancers and has poor prognosis. Bone morphogenetic protein 2 (BMP2) plays important roles in cancer cell signalings (Vecht et al. Oncologist 19:751-9, 2014). Here, we aimed to investigate the correlation of BMP2 with patient prognosis as well as pathological indicators. Immunohistochemistry was used to test BMP2 proteins in 45 gliomas of distinct malignancy grade, and Kaplan-Meier survival analysis was performed to assess prognostic significance. BMP2 protein was also detected in cell lines by Western blot. We observed that BMP2 protein was stained in 44.4% (20 out of 45) of all glioma tissues, including 32.1% of low-grade (I + II) gliomas and 52.9% of high-grade (III + IV) gliomas. Grade IV gliomas potently expressed BMP2 proteins. Western blot showed BMP2 protein expressed in cell lines NHA, A172, T98G, U87, and U251. In addition, BMP2 expression was significantly associated with WHO grade (p = 0.024). According to log-rank test and Cox regression model, BMP2 can be suggested as an independent prognostic factor, apart from WHO grade. Taken together, BMP2 is differently highly expressed in different grades of gliomas and correlated to WHO grade. BMP2 also independently indicates poor prognosis in old glioma patients, which is indicative of an effectively therapeutic target.

ProxyMix: Proxy-based Mixup training with label refinery for source-free domain adaptation.

Due to privacy concerns and data transmission issues, Source-free Unsupervised Domain Adaptation (SFDA) has gained popularity. It exploits pre-trained source models, rather than raw source data for target learning, to transfer knowledge from a labeled source domain to an unlabeled target domain. Existing methods solve this problem typically with additional parameters or noisy pseudo labels, and we propose an effective method named Proxy-based Mixup training with label refinery (ProxyMix) to avoid these drawbacks. To avoid additional parameters and leverages information in the source model, ProxyMix defines classifier weights as class prototypes and creates a class-balanced proxy source domain using nearest neighbors of the prototypes. To improve the reliability of pseudo labels, we further propose the frequency-weighted aggregation strategy to generate soft pseudo labels for unlabeled target data. Our strategy utilizes target features' internal structure, increases weights of low-frequency class samples, and aligns the proxy and target domains using inter- and intra-domain mixup regularization. This mitigates the negative impact of noisy labels. Experiments on three 2D image and 3D point cloud object recognition benchmarks demonstrate that ProxyMix yields state-of-the-art performance for source-free UDA tasks.

Risk factors of early mortality in patients with small cell lung cancer: a retrospective study in the SEER database.

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine cancer with a high risk of early mortality (i.e., survival time less than 1 month). This study aimed to identify relevant risk factors and predict early mortality in SCLC patients. METHODS: A total of 27,163 SCLC cases registered between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) data. Significant independent risk factors were identified by univariate and multivariate logistic regression analyses. Nomograms for all-causes and cancer-specific early death were constructed and evaluated. RESULTS: Age, sex, clinical stage, presence of metastasis (liver and lung), and absence of treatment (surgery, radiotherapy and chemotherapy) were identified for significant association with all-causes and cancer-specific early death. Nomograms based on these predictors exhibited high accuracy (area under ROC curve > 0.850) and potential clinical practicality in the prediction of early mortality. CONCLUSION: We identified a set of factors associated with early mortality from SCLC and developed a clinically useful nomogram to predict high-risk patients. This nomogram could aid oncologists in the administration of individualized treatment regimens, potentially improving clinical outcomes of SCLC patients.

Efficacy comparison between microwave ablation combined with radiation therapy and radiation therapy alone for locally advanced nonsmall-cell lung cancer.

PURPOSE: Comparing the efficacy and complications of microwave ablation (MA) combined with intensity-modulated radiation therapy (IMRT) and IMRT alone for locally advanced peripheral nonsmall-cell lung cancer (NSCLC). METHODS: Retrospective analysis was conducted on 76 patients with locally advanced peripheral NSCLC undergoing chemotherapy and metastatic lymph node radiation therapy from June 2014 to June 2016. Either MA or IMRT was used to treat primary lesions. Thirty-four cases were treated with MA (MA group), 42 cases were treated with IMRT (IMRT group), and comparisons were made of the 1-3-year progression-free survival (PFS) and complications of the two groups. RESULTS: The PFS of the MA group at 1, 2, and 3 years were 70.59% (24/34), 47.06% (16/34), and 35.29% (12/34), and the PFS of the IMRT group at the same intervals were 71.43% (30/42), 52.38% (22/42), and 35.71% (15/42), with no significant difference (χ2 = 0.006, P = 0.936) (χ2 = 0.213, P = 0.645) (χ2 = 0.001, P = 0.970). Radiation-induced lung injury (RILI) occurred in 14.70% (5/34) of MA group patients, which was significantly lower than in the IMRT group 40.48% (17/42), but without grade II or above RILI. CONCLUSION: MA combined with IMRT in the treatment of locally advanced peripheral NSCLC was not inferior to the clinical effect of radiation therapy alone, and radiation lung injury incidence was also lower.

Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression.

OBJECTIVE: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown. METHODS: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays. RESULTS: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked. CONCLUSION: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.

MDR1 single nucleotide polymorphism G2677T/A and haplotype are correlated with response to docetaxel-cisplatin chemotherapy in patients with non-small-cell lung cancer.

BACKGROUND: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy. OBJECTIVES: To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel. METHODS: In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin. RESULTS: The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CONCLUSION: Our findings suggest that the MDR1 2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients.

Randomized controlled trial of lobaplatin plus etoposide vs. cisplatin plus etoposide as first-line therapy in patients with extensive-stage small cell lung cancer.

The majority of previous studies of lobaplatin in small cell lung cancer (SCLC) are small phase I-II studies. The present study aimed to verify the non-inferiority (in terms of efficacy) of lobaplatin plus etoposide (EL) vs. cisplatin plus etoposide (EP) in patients with previously untreated extensive-stage SCLC (ES-SCLC). This phase III non-inferiority randomized clinical trial enrolled patients at 17 sites between September 2010 and May 2013. Patients were randomized to EL (30 mg/m2 lobaplatin on day 1 and 100 mg/m2 etoposide on days 1-3, for 21-day cycles) or EP (80 mg/m2 cisplatin on day 1 and 100 mg/m2 etoposide on days 1-3, for 21-day cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR), toxicity and quality of life (QoL). A total of 234 patients were randomized to the EL (n=122) and EP (n=112) treatment groups. The median PFS, median OS and DCR were 5.1 vs. 5.3 months (P=0.786), 10.6 vs. 9.7 months (P=0.701) and 85.5 vs. 86.7% (P=0.848) in the EL vs. EP groups, respectively. Patients in the EL group had significantly lower frequencies of nephrotoxicity (2.5 vs. 11.7%; P=0.008), nausea (22.3 vs. 40.5%; P=0.003) and vomiting (14.1 vs. 35.1%; P<0.001) than those in the EP group. Overall, EL was not inferior to EP in terms of PFS and OS. The tolerance and QoL of the EL regimen were better than those of the EP regimen. EL is thus an alternative choice for the first-line treatment of ES-SCLC.

MDR1 single nucleotide polymorphisms predict response to vinorelbine-based chemotherapy in patients with non-small cell lung cancer.

BACKGROUND: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. OBJECTIVES: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). METHODS: We determined the genotypes of CYP3A5(*3), MDR1 (2677G-->T at exon 21 and 3435C-->T at exon 26 and their haplotypes) and COX-2 (-1195G-->A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The chi(2) test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. RESULTS: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (-1195G) is likely to result in a better response to vinorelbine (nonsignificant). CONCLUSIONS: Our findings suggest that MDR1 2677G-->T/A and 3435C-->T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.

[Preliminary study of biweekly regimen of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin for advanced gastric cancer].

OBJECTIVE: To evaluate the efficacy and toxicity of a biweekly DOF regimen consisting of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin for advanced gastric cancer. METHODS: The biweekly DOF regimen was administered in 37 advanced gastric cancer patients. Docetaxel, oxaliplatin and leucovorin were given intravenously at a dose of 35 mg/m2, 85 mg/m2 and 200 mg/m2 for 1 h, 2 h and 2 h on D1, respectively, and 5-Fu was administered as continuous intravenous infusion for 48 h at a dose of 1500 mg/m2 on D1 and D2. This regimen was repeated every 2 weeks. The efficacy and toxicity were evaluated after completion of 3 cycles at least. RESULTS: The overall response rate (RR) of this series was 67.6%, complete response rate and partial response rate were 27.0% and 40.5%, respectively. The time to progression (TTP) was 9.2 months, and median survival time (MST) was 13.7 months. The RRs of 11 chemotherpy-naïve patients and 26 patients pre-treated with chemotherapy were 81.8% and 61.5%, respectively. CONCLUSION: Our preliminary results showed that this biweekly combination regimen of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin is effective and tolerable for advanced gastric cancer. However, further investigation of this regimen is mandatory.

[A randomized phase II trial of docetaxel and doxorubicin in treatment for patients with non-small-cell lung cancer who have failed previous platinum-based chemotherapy].

OBJECTIVE: The aim of this study was to evaluate the efficacy, toxicity and safety of doxorubicin combined with domestically produced docetaxel versus with taxotere, and to investigate whether these two regimens result in similar outcomes in the treatment for non-small-cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy. METHODS: Eighty-eight NSCLC patients were enrolled into this clinical phase II trial. The patients randomly received either domestic docetaxel (study arm) or taxotere (control arm) at a dose of 70 mg/m2 on D2, while doxorubicin at a dose of 40 mg/m2 on D1 was administered in both groups. It was repeated every 3 weeks, totally for three cycles. No granulocyte colony-stimulating factor was used to prevent granulocytopenia. The response rate and toxicity were evaluated using World Health Organization toxicity scale and Karnofsky performance status scale. RESULTS: Of the 88 patients, 81 were evaluable in terms of efficacy. There was no complete responder in this series. The response rate (RR) was 17.1% in the study arm versus 7.5% in the control arm, and the clinical benefit rate (CBR) was 80.5% in the study group versus 72.5% in the control group. The most frequent grade 3 or 4 toxicities were neutropenia, leucopenia and gastrointestinal symptoms. Other toxicities such as alopecia and vomiting were mild and generally well tolerated. No fluid retention was noticed. CONCLUSION: The administration of doxorubicin 40 mg/m2 on D1 combined with domestic docetaxel 70 mg/m2 on D2 is proved to be as effective and tolerable as with taxotere. The domestic drug docetaxel may be considered as an alternative for patients with non-small-cell lung cancer who failed previous platinum-based chemotherapy.

Overall Survival Benefit from Trastuzumab-Based Treatment in HER2-Positive Metastatic Breast Cancer: A Retrospective Analysis.

AIM: The purposes of our study were to compare the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) patients with or without trastuzumab treatment and HER2-negative patients, and to explore factors that might predict the survival benefit associated with trastuzumab treatment in HER2-positive breast cancer. PATIENTS AND METHODS: A total of 421 patients with mBC were analyzed in this retrospective study. All patients had first-line chemotherapy with or without trastuzumab. They were classified into 3 groups according to their HER2 status and trastuzumab treatment: HER2-positive mBC patients with or without trastuzumab treatment and HER2-negative patents. RESULTS: Trastuzumab administration in HER2-positive mBC patients significantly prolonged overall survival (33 vs. 26 months; P = 0.003) and led to a 49.8% reduction in death risk. In the subgroup analysis, HER2-positive patients with hormone receptor (HR)-negative status (29 vs. 17 months; P = 0.000) or visceral metastasis (30 vs. 21 months; P = 0.000) had more survival benefit when treated with trastuzumab. CONCLUSIONS: Trastuzumab administration significantly improved the overall survival in HER2-positive mBC patients, who gained a prognosis comparable to that of patients with HER2-negative disease. HR status and metastasis site might be important surrogate makers that predict survival benefit from trastuzumab-based treatment.

The clinical utility and outcomes of microwave ablation for colorectal cancer liver metastases.

In recent years, the microwave ablation (MWA) has been reported to play an important role in the treatment of patients with colorectal liver metastases (CRLM). In this work, 62 cases of patients who received MWA for liver metastases from colon or rectal cancer between Jan 2012 and Jan 2014 were enrolled in this trial. 28 underwent MWA, and 34 were treated with liver resection as control. Perioperative and 60 months of follow-up data were collected to analyze potential adverse effects, concurrent conditions and survival status. Here, we found there were no significant differences between both groups in the baseline level, including gender, size, number and pathological type (all p>0.05). In those patients, the mean hospitalization duration of patients with MWA is 5.9±0.9d, which is significantly different from control (11.8±6.9 d) (p<0.001). Little severe complication was observed in MWA group, while 26.5% (9/34) of patients developed severe complications (p=0.003). Besides, the mean hospitalization cost of patients with MWA was significantly less than that of control (p<0.000). Additionally, we found no statistically significant differences in disease-free survival (DFS) (p=0.156) or overall survival (OS) (p=0.580). In conclusion, MWA may be a safe, economical and competent way to treat inoperable CRLM patients, which has more advantages than liver resection in some degree.

[Docetaxel in the treatment of advanced breast cancer ].

OBJECTIVE: To evaluate the efficacy, toxicity and safety of an new domestic docetaxel in the treatment of pretreated advanced breast cancer. METHODS: Fourty-four breast cancer patients who had failed in first-line chemotherapy were included in this trial. They received docetaxel as the second-line chemotherapy. Docetaxel was administered alone at a dose of 70 mg/m2 every 3 weeks. The use of granulocyte colony-stimulating factor to prevent granulocytopenia was not permitted. The response rate and toxicity were evaluated by World Health Organization toxicity scale and performance status by Karnofsky scale. RESULTS: Of the 41 evaluable patients, 4 achieved complete response and 14 partial remission, with a response rate and clinical benefit rate of 43.9% and 85.4%, respectively. Grade 3 or grade 4 neutropenia developed in 42.9%, alopecia in 7.1% and vomiting in 4.8% of these patients. Fluid retention was not observed in this series. CONCLUSION: Three-week administration of docetaxel alone at a dose of 70 mg/m2 is effective and tolerable. It provides an alternative for the pretreated advanced breast cancer patients.

Hormone receptor status predicts the clinical outcome of human epidermal growth factor 2-positive metastatic breast cancer patients receiving trastuzumab therapy: a multicenter retrospective study.

OBJECTIVES: Trastuzumab, a humanized monoclonal antibody that binds human epidermal growth factor receptor 2 (HER2), dramatically improves the clinical outcomes of HER2-positive breast cancer. Emerging evidence implied that the clinical behavior and sensitivity to targeted agents in HER2-positive breast cancer differed by hormone receptor (HR) status. The objective of this study was to determine the effect of the HR status on survival benefit of HER2-positive metastatic breast cancer when treated with anti-HER2-targeted therapy in People's Republic of China. METHODS: Metastatic breast cancer patients with HER2-positive diseases across six cancer centers in People's Republic of China were retrospectively analyzed in our study. Patients were classified into four groups according to HR/HER2 status and trastuzumab treatment: HER2+/HR+ patients with first-line trastuzumab treatment, HER2+/HR+ patients with no trastuzumab treatment, HER2+/HR- patients with first-line trastuzumab treatment, and HER2+/HR- patients with no trastuzumab treatment. Kaplan-Meier analysis, log-rank test, and multivariate analysis were performed during analysis. RESULTS: A total of 295 patients were included in the final analysis. The median overall survival was 30 months (95% confidence interval: 27.521-32.479). Among patients with HER2+/HR- disease, significant survival benefit was observed when treated with trastuzumab (30 vs 21 months, P=0.000). However, in patients with HER2+/HR+ disease, trastuzumab administration had a survival improvement trend but no significant statistical differences (36 vs 30 months, P=0.258). In the multivariate analysis, HR status was an independent predictor of overall survival and trastuzumab treatment had significantly decreased risk of death in HER2+/HR- patients (hazard ratio =0.330). CONCLUSION: HR status is an independent predictor of overall survival in HER2-positive metastatic breast cancer patients and patients with HER2+/HR- subtype might be associated with more survival benefits when treated with trastuzumab-based regimens.

The crucial role of SRPK1 in TGF-ß-induced proliferation and apoptosis in the esophageal squamous cell carcinomas.

In recent years, transforming growth factor-ß (TGF-ß) and the serine-arginine protein kinase 1 (SRPK1) have been recommended as a key signal mediator that is involved in oncogenesis. However, the mechanisms underlying TGF-ß-SRPK1 pathway-mediated proliferation and apoptosis in the esophageal squamous cell carcinomas (ESCC) have not been well featured till now. We used immunohistochemistry, immunoblotting, and RT-PCR to assess the expression of SRPK1 in 120 cases of ESCC samples and cell lines. Subsequently, some in vitro assays were also applied where cells were administrated with TGF-ß. We found that SRPK1 was highly expressed in ESCC tissues and acts as an independent prognostic factor for ESCC patients. In vitro studies indicated that overexpression of wild-type SRPK1 promoted ESCC cell proliferation, while overexpression of the kinase-dead mutant of SRPK1 or RNA interference against SRPK1 suppressed cell growth and enhanced apoptosis. The knockdown of SRPK1 also inhibited subcutaneous xenografts' growth of ESCC cells in nude mice. Furthermore, Western bolt analysis showed SRPK1 can activate Akt phosphorylation and inhibit JNK phosphorylation. In conclusion, SRPK1 mediates TGF-ß-induced proliferation and apoptosis by regulating AKT and JNK in ESCC, which indicates TGF-ß-SRPK1 pathway may be suggested as a useful target to affect the progression of ESCC.

CYP450 polymorphisms predict clinic outcomes to vinorelbine-based chemotherapy in patients with non-small-cell lung cancer.

CYP2C19*2(G681A), CYP2C19*3(G636A), CYP2D6*4(C188T), CYP2D6*2(C2938T, G4268C), CYP3AP1*3- G44A and CYP3A5*3(A22893G) are the most common polymorphisms detected among Chinese that may influence the efficacy of vinorelbine-based therapies to treat non-small-cell lung cancer (NSCLC). We detected the genotypes of these polymorphisms by PCR-RFLP in 59 patients with NSCLC and assessed their responses to vinorelbine. CYP2D6*4(C188T), CYP3AP1*3 (G -44 A) and CYP3A5*3 were found to be associated with response to vinorelbine. For the 2D6*4 polymorphism, the 18 of 32 (56.25%) patients with homozygous (C/C) responded to this therapy, while 6 of 27 (22.22%) of those heterozygous (C/T) at this site responded. (chi2=5.68, p < 0.05) For the 3AP1*1/*3 polymorphism, 12 of 42 (28.57%) patients with homozygous (A/A) responded, while 12 of 17 (70.59%) with heterozygous (A/G) and homozygous (G/G) responded (chi2=7.19, p < 0.01). CYP3A5*3 polymorphism has a result corresponding to 3AP1*3 polymorphism. Other polymorphisms were not associated with response to vinorelbine. No significant difference in toxicity and survival was observed according to SNP genotype.