Phase II Study of Weekly Nanoparticle Albumin-Bound Paclitaxel as Second- or Third-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) are poor due to limited treatment options. OBJECTIVE: We conducted a multicenter, single-arm phase II study to prospectively assess the efficacy and safety of weekly nab-PTX in patients with advanced NSCLC with failed cytotoxic chemotherapy. METHODS: Patients with advanced NSCLC having adequate organ functions with a performance status of 0-1 were enrolled. A 100 mg/m2 dose of nab-paclitaxel was administered on days 1, 8, and 15 of a 28-day cycle. Primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), toxicity profile, progression-free survival (PFS), and overall survival (OS). RESULTS: Between September 2013 and May 2016, 35 patients were enrolled. The ORR was 31.4%, and the DCR was 74.3%. The median PFS was 3.6 months, and the median OS was 11.4 months. The most common grade 3 or 4 toxicities included neutropenia (54.3%), leukopenia (42.9%), and anemia (11.4%). Two patients discontinued chemotherapy due to pneumonitis. CONCLUSIONS: Nab-PTX may be a later-line chemotherapeutic option for previously treated advanced NSCLC.

Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy.

BACKGROUND: In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. METHODS: Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. RESULTS: Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). CONCLUSIONS: In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS.

High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma.

BACKGROUND: Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients. METHODS: Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy. RESULTS: This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36-75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS. CONCLUSIONS: Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.

[Lung Segmentectomy Using Video-assisted Thoracic Surgery for Lung Cancer in a Patient with Situs Inversus Totalis].

The case was 83-year-old man who had complete situs inversus, and was pointed out to have peripheral adenocarcinoma with the size of 1.8 cm at the left upper lobe( S3). Because of severe emphysema and other multiple comorbidities, left S3 segmentectomy with hilar lymph node sampling was performed using video-assisted thoracic surgery (VATS). Preoperatively, the simulation of operation was performed using the 3 dimension computed tomography images of pulmonary arteriovenous and bronchus (3DCTAB). Postoperative course was uneventful. 3DCTAB was thought to be useful in understanding the anatomical location of pulmonary arteriovenous and bronchus directly, and in performing segmentectomy in the case of situs inversus like this.

Comparison of the efficacy of radiotherapy between postoperative mediastinal lymph node recurrence and stage III disease in non-small cell lung cancer patients.

PURPOSE: It is unknown if local treatment is equally effective in non-small cell lung cancer (NSCLC) patients with postoperative mediastinal lymph node recurrence or primary stage III disease. The purpose of this study was to investigate the effectiveness of radiotherapy, with or without chemotherapy, in patients with postoperative mediastinal lymph node recurrence. METHODS: Patient characteristics, treatment response and survival were compared between NSCLC patients with mediastinal lymph node metastases treated between 2002-2009 by radiotherapy alone or by chemoradiotherapy (group A, N=33) and those with primary stage III disease (group B, N = 157). RESULTS: Men accounted for 60.6% of group A and 78.9% of group B (p=0.04 patients). ECOG performance status 0 was detected in 78.7% of group A and 57.3% of group B (p=0.02). The response rates in groups A and B were 66.6 and 72.3%, respectively (p=0.64). Progression-free survival (PFS) was similar between groups A and B (median 15.0 vs 11.0 months; hazard ratio [HR] 0.78; 95% CI 0.51-1.20; p=0.26). However, overall survival (OS) was better in group A than in group B (median 67.0 vs 39.0 months; HR 0.56; 95% CI 0.29-0.97; p=0.03). Postoperative PFS (median 12.5 vs 19.0 months; HR 1.50; 95% CI 0.64-3.49; p=0.34) and OS (median, 67.0 vs 60.0 months; HR 1.22; 95% CI 0.36-4.14; p=0.74) were similar between the group A treatments (radiotherapy and chemoradiotherapy, respectively). CONCLUSION: Postoperative mediastinal lymph node recurrent NSCLC demonstrated distinctive features including better OS compared to patients with primary stage III disease, despite similar response rates and PFS.

[A case of clinically diagnosed eosinophilic bronchiolitis].

A 71-year-old man was referred to our hospital because of an intractable productive cough. Although he was treated for bronchial asthma, the symptom did not improve. Furthermore, since he developed progressive dyspnea and hypoxemia, he was admitted to our hospital. Marked eosinophilia in a blood test and sputum, poorly defined centrilobular nodules throughout the bilateral lung fields in a chest CT scan, and mixed ventilatory impairment in a spirometric test were revealed. Thoracoscopic lung biopsy and bronchoalveolar lavage were not conducted because of progressive respiratory failure. Therefore, we clinically diagnosed eosinophilic bronchiolitis, and immediately administered oral prednisolone (30 mg daily). His symptoms and examination findings rapidly improved. This case suggests that eosinophilic bronchiolitis should be taken into consideration for differential diagnoses of eosinophilic lung disease and obstructive lung disease, and marked eosinophilia in sputum may be one of the useful tools for diagnosis of this disease when invasive examinations are inadequate.

Efficacy and safety of platinum combination chemotherapy re-challenge for relapsed patients with non-small-cell lung cancer after postoperative adjuvant chemotherapy of cisplatin plus vinorelbine.

BACKGROUND: There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. METHODS: Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. RESULTS: Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). CONCLUSION: Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC.

[High-grade fetal adenocarcinoma of the lung; report of a case].

82-year-old man was admitted with an abnormal shadow on the chest roentgenogram. Computed tomography showed a 2.8 x 2.4 cm solid tumor in S3 of the left lung. Transbronchial lung biopsy revealed adenocarcinoma and a left upper lobectomy (ND2a-1) was performed. The tumor consisted mainly of tall columnar clear cells, and no morules were found. Immunohistochemically, the tumor was positive for alpha-fetoprotein (AFP) and p53. Accordingly, we made the histological diagnosis of high-grade fetal adenocarcinoma of the lung, pT2N0M0, stage IB. The patient was not received adjuvant therapy and has been doing well without any tumor recurrence for 3 months postoperatively.

[A case of sarcoidosis with bilateral pleural effusion treated with high-dose steroids].

A 25-year-old man was admitted with elevated fever, dyspnea, cough, dorsal chest pain, and multiple nodular shadows and pleural effusion found on chest X-ray films. There were multiple swollen superficial lymph nodes, and non-caseating epithelioid cell granulomas with Langhans giant cells were detected on a biopsy specimen of a right inguinal lymph node. Bronchoscopy findings demonstrated mucosal irregularity, telangiectasia and small nodules, and another biopsy specimen was similar to that of the inguinal lymph node. The number of lymphocytes and the CD4/CD8 ratio were elevated in his bronchoalveolar lavage fluid, and serum ACE and lysozymes levels were also elevated. These findings are compatible with sarcoidosis. Although his symptoms and pleural effusion improved with the administration of 30 mg/day prednisolone (PSL), these findings recurred after about 4 weeks. Therefore, we increased the PSL dose to 60 mg/day, and his symptoms, pleural effusions and laboratory data improved again. There were no signs of relapse after tapering and discontinuance of PSL.

Epigenetic inactivation of the thyroid hormone receptor beta1 gene at 3p24.2 in lung cancer.

BACKGROUND: Frequent allelic loss on chromosome 3p in various human cancers suggests the presence of tumor suppressor genes in this region. The thyroid hormone receptor beta1 (TRbeta1) gene is located at 3p24.2, where allelic loss frequently occurs in lung cancer, and aberrant TRbeta1 methylation was observed in several human cancers. METHODS: We examined the expression, mutation, and promoter methylation of TRbeta1 in 18 small cell lung cancer (SCLC) and 29 non-small cell lung cancer (NSCLC) cell lines by reverse-transcription polymerase chain reaction (RT-PCR), direct sequencing, or methylation-specific PCR. Four lung cancer cell lines lacking TRbeta1 expression were treated with 5-aza-2-deoxy-cytidine and/or trichostatin-A, and the TRbeta1 expression was determined by RT-PCR. We also examined the TRbeta1 methylation in 116 NSCLC surgical specimens and analyzed the correlation between methylation status and clinicopathological parameters or mutations of KRAS and EGFR. RESULTS: TRbeta1 expression was absent in 61% of SCLCs and 48% of NSCLCs, and 67% of SCLCs and 45% of NSCLCs carried TRbeta1 promoter methylation, while no somatic mutation was found in all cell lines. TRbeta1 methylation status was significantly associated with loss of TRbeta1 expression. TRbeta1 expression was restored by treatment with 5-aza-2-deoxy-cytidine and/or trichostatin-A in four cell lines. TRbeta1 methylation was found in 47% of NSCLC surgical specimens; however, the methylation was not significantly associated with any clinicopathological parameters or mutations of KRAS and EGFR. CONCLUSIONS: This is the first study to demonstrate epigenetic inactivation of TRbeta1 through aberrant methylation in lung cancer, while TRbeta1 mutations are not common in lung cancer.

[A case of non-small cell lung cancer responding to S-1 over a year].

A 71-year-old woman was admitted to our hospital, because of an abnormality on her chest radiograph findings. After extensive examination, she was diagnosed with primary lung adenocarcinoma (cT4N2M1, stage IV). She was treated by carboplatin+gemcitabine, gefitinib and docetaxel and the responses were stable disease in any treatment. As the fourth-line treatment, she received oral chemotherapy using S-1 at 100 mg/day (80 mg/m2 day) for 28 days, followed by withdrawal for 14 days. Tumor size was reduced 29.2% after 1 course, 62.5% after 5 courses and 83.3% after 10 courses (14 months). Hematologic and non-hematologic toxicities were mild with the S-1 administration. We experienced a case of continuation of tumor shrinkage over a year without serious adverse events by S-1 treatment. Therefore, oral administration of S-1 could be useful for the treatment of recurrent non-small cell lung cancer over a long time.

Usefulness of FDG-PET for early prediction of the response to gefitinib in non-small cell lung cancer.

Increased tumor uptake of (18)F-fluorodeoxyglucose (FDG) measured by positron emission tomography (PET) reflects glucose metabolism and proliferative activity of tumor cells. We conducted a study to assess the usefulness of FDG-PET for early prediction of the response to gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in advanced non-small cell lung cancer (NSCLC). Five NSCLC patients underwent FDG-PET to evaluate changes in FDG uptake at day 2 and 4 weeks after the initiation of gefitinib therapy compared with FDG-PET prior to therapy. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of the target lesions, which were assessable by conventional CT. Based on the CT evaluation, two patients exhibited a partial response (PR), two patients had stable disease (SD) with a minor response, and one patient had progressive disease (PD). In patients with PR and SD, SUVmax decreased by 61+/-18% (standard deviation) and 59+/-12%, respectively, on day 2, and by 26+/-6 and 43+/-10%, respectively, at 4 weeks after the initiation of gefitinib. Two patients with SD had decreased FDG uptake within 2 days of initiation of therapy, and achieved progression-free survival (PFS) of more than 12 months. In contrast, SUVmax increased up to 153+/-21% at 2 days and 232+/-73% at 4 weeks in a patient with PD. The present preliminary study suggests that FDG-PET may be able to predict response to gefitinib in the early stage of therapy in patients with advanced NSCLC and may have a potential prognostic role.

Primary Sjogren's syndrome complicated by bilateral pleural effusion.

Sjogren's syndrome can cause many organic changes, but is rarely accompanied by pleuritis. We report a 65-year-old patient with primary Sjogren's syndrome who developed bilateral pleuritis with moderately large effusions. He was diagnosed as having Sjogren's syndrome, based on xerophthalmia, xerostomia, positive results for anti-Sjogren's syndrome (anti-SS-A/SS-B) antibodies, the Schirmer test and biopsy findings in the minor salivary glands. The pleural fluid was lymphocyte rich and contained high levels of anti-SS-A/SS-B antibodies. There was no evidence of infection, malignancy or other collagen diseases which cause pleuritis. We conclude that this case adds to the eight previously published reports of primary Sjogren's syndrome complicated by pleural effusion.

A phase II study of biweekly gemcitabine and carboplatin in completely resected stage IB-IIIA non-small cell lung cancer.

PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of biweekly gemcitabine and carboplatin combination treatment in patients with resected non-small cell lung cancer (NSCLC). METHODS: Patients with completely resected stage IB to IIIA NSCLC were treated with four cycles of gemcitabine (1000 mg/m2, days 1 and 15) plus carboplatin [area under the time-concentration curve (AUC) 5 mg/mL/min, day 1] every 4 weeks as adjuvant chemotherapy. RESULTS: Forty-three patients were enrolled in this study. The median number of treatment cycles was four. The completion rate of chemotherapy was 79.1%. Major grade 3/4 hematological adverse events included leukocytopenia (27.9%) and neutropenia (53.5%), whereas non-hematological toxicities were generally mild. Ten patients (23.3%) required chemotherapy treatment schedule delay, and one patient required one dose level reduction because of drug fever. Median disease-free survival was 78.6 months [95% confidence interval (CI) 39.5-not reached (NA)] and median overall survival was not reached (95% CI 83.7-NA). CONCLUSIONS: Biweekly administration of gemcitabine and carboplatin is effective and well tolerated for patients with completely resected NSCLC as an adjuvant chemotherapy.

Characteristics and outcomes of patients with EGFR-mutation positive non-small-cell lung cancer receiving gefitinib beyond radiological progression.

BACKGROUND: This study aimed to analyze the characteristics and outcomes of patients suffering from non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor mutations (EGFRm+) receiving gefitinib who remained clinically stable following confirmation of progressive disease (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) (R-PD) and identify those who benefited from tyrosine kinase inhibitor therapy beyond PD. RESEARCH DESIGN AND METHODS: The clinical courses of patients with EGFRm+ advanced NSCLC who received first-line gefitinib were investigated. Clinical PD (C-PD) was defined as one or more of the following: (1) symptomatic PD, (2) worsening performance status resulting from PD, (3) threat to a major organ(s), or (4) unequivocal multiorgan PD. RESULTS: Of 529 patients, 258 experienced R-PD without C-PD. Among 258 patients, 91 received gefitinib beyond R-PD. Females were more likely to receive gefitinib beyond R-PD and exhibit a longer time from R-PD to C-PD than males (median days, 175 vs. 79.5). Survival beyond R-PD tended to be longer for elderly patients who received gefitinib beyond PD than for those who did not (median days, 458 vs. 336), but this was not the case for non-elderly patients (median days, 481 vs. 487). CONCLUSIONS: Some patients may benefit from continuation of gefitinib beyond PD.

Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers.

RASSF2, a member of the RAS association domain family 1 (RASSF1), is a candidate tumor suppressor gene (TSG) that is silenced by promoter hypermethylation in several human cancers. In this study, we examined the expression of RASSF2 mRNA and the promoter methylation status in lung cancer cell lines and in tumor samples of 106 primary non-small cell lung cancers (NSCLCs) by methylation-specific PCR. RASSF2 expression was absent in 26% of small cell lung cancers (SCLCs; n=27 lines) and 50% of NSCLCs (n=42 lines). Promoter methylation of RASSF2 was found in 18% of the SCLC cell lines (n=22) and 62% of the NSCLC cell lines (n=26), and the methylation status was tightly associated with the loss of RASSF2 expression. RASSF2 expression was restored by treatment with 5-aza-2-deoxycytidine and/or trichostatin-A in the NSCLC cell lines which were absent of the expression. RASSF2 methylation was found in 31% of primary NSCLC tumors, and methylation was more frequent in the specimens from non-smokers (18 of 40, 45%) than in the specimens from smokers (15 of 66, 23%, P=0.014). We also examined the association of RASSF2 methylation with mutations of KRAS and EGFR and with promoter hypermethylation of RASSF1A; however, we could not find a significant association between RASSF2 methylation and these genetic and epigenetic changes. Our results indicate that aberrant methylation of the RASSF2 gene with the subsequent loss of RASSF2 expression plays an important role in the pathogenesis of lung cancers.

Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy.

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of non-small cell lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stage III/IV NSCLC whose tumors carried EGFR mutations, irrespective of previous chemotherapy. EXPERIMENTAL DESIGN: Genomic DNA was extracted from tumor specimens and EGFR mutations in exons 19 and 21 analyzed by direct sequencing. Patients with stage III/IV NSCLC whose tumors had the EGFR mutations received gefitinib (250 mg/day orally). Response, toxicity and survival data were assessed. RESULT: From November 2004-May 2006, 21 patients with EGFR mutations received gefitinib (median age: 59 years; 17 females; 19 non-smokers; all had adenocarcinomas). Two patients discontinued gefitinib and withdrew from the study 3 weeks after gefitinib initiation (interstitial pneumonitis, 1 patient; facial acne, 1 patient). Of 19 patients, 3 achieved complete response, 13 exhibited partial response and 3 had stable disease. Response and disease control rates were 76% (95% confidence interval [CI] 53-92) and 90% (95% CI 70-99), respectively. The most common adverse event was skin toxicity (67%); however, no grade 4 skin toxicities were seen. Ten patients relapsed and three died at a median follow-up period of 12.6 months (range 5.6-23.8 months); median progression-free survival was 12.9 months. CONCLUSION: Analysis of tumor EGFR mutations in patients with NSCLC could be used to identify patients suitable for treatment with gefitinib to obtain optimum response and disease control rates.

[A case of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in a young adult successfully treated with gefitinib].

The patient was a 39-year-old woman admitted with complaints of fever, clubbed fingers and arthralgia. A chest roentgenogram and chest computed tomographic scan revealed a mass in the left lower lobe. Transbronchial lung biopsy was performed, and a diagnosis of moderately differentiated adenocarcinoma was made. Physical examination confirmed finger clubbing in both hands. Bone scintigram showed marked accumulation of 99mTc-MDP in the long bones, bones of the elbows, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in young adult. The patient had fever and disturbance of gait of arthralgia on admission, and was treated with an oral non-steroidal anti-inflammation drug (NSAID). Advanced non small cell lung cancer (clinical stage T2 N3 M1, Stage IV) was then diagnosed. Gefitinib was administered after EGFR mutation was found in the tumor specimen. NSAID therapy alleviated the fever and arthralgia. After starting gefitinib and discontinuing the NSAID, She had kept a remission of rational symptom with cytoreductive effect. The abnormal findings of bone scintigrams subsequently disappeared and the patient's serum ICTP dropped.

[A case of multidrug-resistant non-small cell lung cancer responding to TS-1].

A 72-year-old man was admitted to our hospital, complaining of exertional breathlessness. Chest radiograph revealed a right pleural effusion. Cytology for pleural effusion revealed adenocarcinoma; thus, he was diagnosed with advanced lung cancer (clinical stage T 4 N 0 M 0, Stage IIIB). Since tumor recurrence occurred despite CBDCA+gemcitabine, docetaxel, gefitinib and vinorelbine administrations, he received fifth-line oral chemotherapy using TS-1 at 120 mg/day (80 mg/m(2)/day) for 28 days, followed by withdrawal for 14 days. Chest computed tomography showed a partial response. Hematologic and non-hematologic toxicities were mild with the TS-1 administration. TS-1 could be an effective agent for treatment of multidrug-resistant non-small cell lung cancer.

Prognostic effect of class III ß-tubulin and Topoisomerase-II in patients with advanced thymic carcinoma who received combination chemotherapy, including taxanes or topoisomerase-II inhibitors.

Class III ß-tubulin (TUBB3) and Topoisomerase-II (topo-II) are considered to be the predictors of therapeutic efficacy and outcome in several types of human neoplasm. However, whether TUBB3 or topo-II may predict the response to combination chemotherapy and prognosis in patients with advanced thymic carcinoma (ATC) remains unclear. The aim of the present study was to investigate the prognostic significance of TUBB3 and topo-II expression levels in ATC. A total of 34 patients with ATC who received combination chemotherapy were enrolled in the present study. Immunohistochemical analysis was used to examine the expression of TUBB3, topo-II and Ki-67 in tumor specimens obtained by surgical resection or biopsy. TUBB3 and topo-II were highly expressed in 38 and 53% of the tumors, respectively. Progression-free survival (PFS) was significantly shorter in patients with high levels of TUBB3 compared with those with low levels of TUBB3 (P<0.01), whereas no significant difference in PFS between patients with high and low topo-II expression levels was observed (P=0.31). Patients with overexpression of TUBB3 or topo-II exhibited significantly shorter overall survival rates (OS) compared with those patients with low levels of expression of these proteins (TUBB3; P=0.01, topo-II; P=0.01). Multivariate analysis demonstrated that a high level of TUBB3 expression was an independent unfavorable prognostic factor for OS, and a high level of topo-II expression tended to correlate with poor prognosis without statistical significance. Additionally, a subset analysis demonstrated that the treatment with taxanes, but not topo-II inhibitors, tended to prolong OS in patients with TUBB3 overexpression and there was significant survival advantage of chemoradiotherapy over chemotherapy in patients with topo-II overexpression. It was revealed that an enhanced expression of TUBB3 or topo-II was clearly associated with clinical outcomes in patients with ATC who received combination chemotherapy, including taxanes or topo-II inhibitors, suggesting the prognostic significance of these markers.