Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Treatment and Salvage Chemotherapy in EGFR-Mutated Elderly Pulmonary Adenocarcinoma Patients.

BACKGROUND: Lung cancer is frequently a disease of elderly patients. However, these patients are often treated less actively owing to a higher comorbidity rate and poor performance status. The efficacy of different treatments in elderly patients with epidermal growth factor receptor (EGFR)-mutated lung cancer is still unknown. MATERIALS AND METHODS: We retrospectively reviewed the records of our pulmonary adenocarcinoma patients treated between 2010 and 2013. Data on patient age, type of tumor EGFR mutation, response to first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, type of salvage chemotherapy, and efficacy of EGFR-TKI and salvage chemotherapy were collected. RESULTS: In all, 473 of 1,230 stage IV adenocarcinoma patients had an EGFR mutation, and 330 of them received first-line TKI treatment. Of the 330 patients, 160 were ≥70 years old (elderly group) and 170 were <70 years old (younger group). The response rate and progression-free survival (PFS) with first-line TKI treatment were not significantly different. The elderly group had shorter median survival. A total of 107 patients received salvage chemotherapy after first-line EGFR-TKI treatment: 45 in the elderly group and 62 in the younger group. Their response rate and PFS were not significantly different; however, the younger group had longer median survival. Additional subgroup analysis showed that younger patients who received platinum-based chemotherapy or combination chemotherapy had better median survival than did the elderly patients. The PFS was longer among younger patients receiving a platinum-based regimen than that among the elderly patients. CONCLUSION: Elderly patients with disease progression after first-line EGFR-TKI treatment can receive chemotherapy and have a response rate similar to that of younger patients. IMPLICATIONS FOR PRACTICE: The aim of the present study was to investigate the efficacy of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in elderly patients and the outcomes of subsequent salvage chemotherapy after disease progression. The most important finding was that elderly patients with disease progression after first-line EGFR-TKI treatment can receive salvage chemotherapy and have a response rate similar to that of younger patients who received salvage chemotherapy.

Plasma soluble vascular endothelial growth factor receptor-1 levels predict outcomes of pneumonia-related septic shock patients: a prospective observational study.

INTRODUCTION: Despite recent advances in the management of septic shock, mortality rates are still unacceptably high. Early identification of the high-mortality risk group for early intervention remains an issue under exploration. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR1) and urokinase plasminogen activator (uPA) have diverse effects in the pathogenesis of sepsis, which involve pro-inflammation, anti-inflammation, endothelial cell repair, and vascular permeability change. Their roles in predicting mortality and organ dysfunction remain to be clarified. METHODS: Pneumonia-related septic shock patients from medical intensive care units were enrolled for this prospective observational study. We also included 20 patients with pneumonia without organ dysfunction for comparison. Plasma levels of VEGF and sVEGFR1 and uPA activity within 24 hours of shock onset were measured. We compared plasma levels of these biomarkers with APACHE II scores between subgroups of patients, and evaluated their predictive value for 28-day mortality and organ dysfunction. RESULTS: A total of 101 patients, including 81 with pneumonia-related septic shock and 20 with pneumonia without organ dysfunction, were enrolled. Non-survivors of septic shock had significantly higher plasma sVEGFR1 levels (659.3 ± 1022.8 vs. 221.1 ± 268.9 pg/mL, respectively, P < 0.001) and uPA activity (47.2 ± 40.6 vs. 27.6 ± 17.2 units, respectively, P = 0.001) when compared with those of the survivors. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients with higher levels of sVEGFR1 (P < 0.001) and uPA activity (P = 0.031). In Cox regression analysis, plasma sVEGFR1 level was independently associated with, and best predicted, the 28-day mortality of septic shock (HR: 1.55, 95% CI: 1.05-2.30). Plasma sVEGFR1 level and uPA activity had good correlation with renal dysfunction, metabolic acidosis, and hematologic dysfunction; their levels significantly increased when the number of organ dysfunctions increased. In multivariate analysis, plasma sVEGFR1 level (HR: 2.82, 95% CI: 1.17-6.81) and uPA activity (HR: 2.75, 95% CI: 1.06-7.13) were independent predictors of the presence of concomitant multi-organ dysfunction. The predictive value of VEGF for mortality and organ dysfunction was limited in pneumonia-related septic shock patients. CONCLUSIONS: High plasma sVEGFR1 level in the early stage of pneumonia-related septic shock independently predicted 28-day mortality and multi-organ dysfunction.

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10-26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10-3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

Efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia.

Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent in vitro and in vivo activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant Streptococcus pneumoniae. Patients with mild to moderate CAP (n = 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.

Decoy receptor 3 levels in peripheral blood predict outcomes of acute respiratory distress syndrome.

RATIONALE: Acute respiratory distress syndrome (ARDS), a serious inflammatory reaction to acute lung injury, is associated with high mortality rates. Decoy receptor (DcR) 3 is a soluble protein with immunomodulatory effects. Biomarkers that reliably predict outcomes in ARDS are not currently available. OBJECTIVES: Comparing DcR3 with the Acute Physiology and Chronic Health Evaluation (APACHE) II scores and three other plasma markers to explore the association of DcR3 and the clinical outcome in ARDS. METHODS: Eighty-eight patients with ARDS were studied. Baseline APACHE II scores and clinical data were recorded. Plasma levels of DcR3, soluble triggering receptor expressed on myeloid cells (sTREM)-1, tumor necrosis factor (TNF)-alpha, and IL-6 were measured on Day 1 and later time points, and correlated with the survival status on Day 28 after the onset of ARDS. For validation, 59 patients with ARDS from another medical center were studied. MEASUREMENTS AND MAIN RESULTS: Among the biomarkers evaluated, only DcR3 discriminated the survivors and nonsurvivors at all time points in the first week of ARDS. DcR3 independently associated with and best predicted the 28-day mortality of patients with ARDS. Plasma DcR3 levels most correlated to multiple-organ dysfunction and ventilator dependence. Compared with survivors, the nonsurvivors had higher DcR3 levels regardless of the APACHE II scores. Kaplan-Meier survival analysis showed higher mortality in patients with ARDS with higher DcR3 levels. The outcome prediction of patients with ARDS by plasma DcR3 levels was recapitulated by the validation cohort. CONCLUSIONS: High plasma DcR3 levels correlate with development of multiple-organ dysfunction and independently predict the 28-day mortality in patients with ARDS.

A phase II randomized study of vinorelbine alone or with cisplatin against chemo-naïve inoperable non-small cell lung cancer in the elderly.

PURPOSE: Our aim here was to determine whether or not the addition of cisplatin into vinorelbine (V) treatment is an appropriate regimen for physically fit chemo-naïve non-small cell lung cancer (NSCLC) patients aged 70 or older. PATIENTS AND METHODS: Patients were randomized into vinorelbine (V) or vinorelbine plus cisplatin (VP) treatment arms. Treatment consisted of vinorelbine 25 mg/m(2) intravenous infusion (i.v.) on days 1 and 8 every 3 weeks (V arm), or vinorelbine 22.5 mg/m(2) i.v. on days 1 and 8 plus cisplatin 50 mg/m(2) i.v. on day 1 every 3 weeks (VP arm). RESULTS: Sixty-five patients were enrolled from May 2005 to December 2006, including 31 who received V treatment and 34 who received VP treatment. Objective response rates were 16.1% in V and 32.4% in VP (p=0.009). Control rates were 51.6% in V and 82.4% in VP (p=0.008). Myelosuppression was more common and severe in the VP arm. Any grade of anemia and neutropenia was significantly higher in the VP arm (p=0.001 and 0.009, respectively). Fatigue sensation was more common and severe in the VP arm (p=0.032). Median time to disease progression was 3.1 months in the V arm and 5.2 months in the VP arm (p=0.0303). The 1-year survival rate was 50.9% in the V arm and 47.2% in the VP arm. CONCLUSIONS: Adding cisplatin to vinorelbine treatment is feasible in elderly patients, and has a better response rate and longer median time to disease progression. However, both statistically significantly higher toxicity and no survival advantage for the combination treatment was observed.

Phase II randomized study of weekly docetaxel alone or plus UFUR treatment in non-small cell lung cancer patients who failed previous chemotherapy.

PURPOSE: This study aimed to assess the feasibility and efficacy of adding UFUR (UFT, tegafur/uracil) into weekly docetaxel treatment for non-small cell lung cancer (NSCLC) patients who failed previous platinum-based chemotherapy. METHODS: Patients were randomized into two arms: docetaxel 40mg/m(2) intravenous infusion (IV) on days 1 and 8 of every 3 weeks (arm D), and docetaxel 35mg/m(2) IV on days 1 and 8 plus daily oral UFUR 150mg/m(2) of every 3 weeks (arm DU), with arm D as a control arm. Treatment was given to a maximum of 6 cycles and carried out in the outpatient clinic. RESULTS: From January 2005 to March 2006, 48 patients were enrolled and randomized into the study, with 24 patients in each arm. The mean number of cycles of treatment was 4 in the D arm and 3.5 in the DU arm. Objective response rates were 29.2% in the D arm and 8.3% in the DU arm (p=0.067). Toxicities were few and mild in degree in both arms. Median time to disease progression was 4.5 months in the D arm and 2.1 months in the DU arm (p=0.4682). Median survival time was 10.9 months in the D arm and 15.2 months in the DU arm (p=0.8442). CONCLUSIONS: The addition of UFUR to weekly docetaxel treatment did not improve response rate and time to disease progression in NSCLC patients who failed previous platinum-based chemotherapy.

High efficacy of erlotinib in Taiwanese NSCLC patients in an expanded access program study previously treated with chemotherapy.

PURPOSE: Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. METHODS: Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150mg/day till disease progression. RESULTS: From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p=0.033), adenocarcinoma/BAC (p=0.0027), female (p=0.0013), aged less than 65 years (p=0.0115), stage IV (p=0.0492), patients with skin rash (p=0.0216), and a higher grade of skin rash (p=0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3-4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. CONCLUSIONS: This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.

Symptomatic ocular metastases in lung cancer.

BACKGROUND AND OBJECTIVE: A survey was carried out of ocular manifestations of lung cancer. METHODS: A retrospective analysis was performed of all lung cancer patients diagnosed between 1991 and 2005 at Taipei Veterans General Hospital, Taipei, Taiwan. RESULTS: Sixteen lung cancer patients with symptomatic ocular metastases were identified. The incidence was less than 1%. The low incidence among these patients contrasts with previous reports of an incidence of about 6-7%, and suggests that most patients with ocular metastasis may be asymptomatic and remain undiagnosed. The most frequent ocular symptoms were changes in visual acuity. Metastases most frequently originated from adenocarcinomas and the choroids were the most common sites of metastases. Ten of the 16 ocular metastases were early events, identified prior to or at the initial diagnosis of the lung cancer. Only three of the 16 ocular metastatic events presented as solitary distant metastases. CONCLUSION: Although symptomatic ocular metastases are rare, they should be considered in lung cancer patients presenting with alterations in visual acuity.

Peritoneal carcinomatosis in lung cancer.

BACKGROUND AND OBJECTIVE: A survey was carried out of peritoneal carcinomatosis (PC) in lung cancer. METHODS: A retrospective analysis was conducted of all lung cancer patients with malignant ascites diagnosed between 1990 and 2005 at a general hospital in Taiwan. RESULTS: There were 30 lung cancer patients with documented PC. The most frequent abdominal symptom was abdominal distension. The most common histological type of lung cancer with PC was adenocarcinoma. Eighty per cent of the patients developed malignant pleural effusions before the diagnosis of PC. The median survival after diagnosis of PC was 15 days. Two adenocarcinoma patients with PC benefited from treatment with gefitinib. CONCLUSIONS: Further study is warranted to investigate the use of gefitinib in treatment of patients with lung adenocarcinoma and PC.

Increasing drug resistance of Mycobacterium tuberculosis isolates in a medical center in northern Taiwan.

BACKGROUND/PURPOSE: This retrospective study was conducted to evaluate the drug resistance patterns of Mycobacterium tuberculosis in a medical center in northern Taiwan between 2003 and 2004 in comparison to those reported in 1990-1992. METHODS: A total of 611 non-duplicate M. tuberculosis isolates from culture-proven tuberculosis (TB) cases were tested for drug susceptibility against five first-line anti-TB drugs in a clinical mycobacterial laboratory using the agar proportional method for isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and streptomycin (SM). The Wayne assay, which measures the activity of pyrazinamide (PZA), was used for PZA susceptibility testing. RESULTS: Of 611 patients, including 510 males and 101 females, 70.2% of patients were older than 65 years. A total of 339 isolates (55.5%) were resistant to one or more drugs. Isolates from patients aged <25 years showed a significantly higher drug resistance rate (79.2%) compared with other age groups (p=0.0312). Single-drug resistance was observed in 97 (15.9%) of all isolates. Monoresistance to PZA (8.0%) was most frequent, followed by INH (5.1%), RIF (0.5%), EMB (1.6%), and SM (0.7%). Among the polydrug resistant isolates (PDR-TB), resistance rates were 35.5% for INH and 27.0% for RIF. One hundred and fifty-nine isolates (26.0%) were resistant to both INH and RIF (multidrug-resistant [MDR] TB); 94.6% of RIF-resistant isolates were also resistant to INH. The overall drug resistance rates and percentages of PDR-TB and MDR-TB increased over the 12-year study period (p<0.001). Based on medical records, primary cases were identified in 486 (84.7%) out of 574 patients, and resistance to any drug was identified in 268 (55.1%) patients, of which 130 (26.7%) were MDR-TB. Among the 88 with recurrent TB, 54 (61.4%) were resistant to at least one drug, and MDR-TB was identified in 29 (33.0%) patients. A history of previous anti-TB therapy was a significant factor for overall drug resistance, PZA monoresistance, PDR-TB, and MDR-TB (p<0.001). CONCLUSION: The emergence of M. tuberculosis isolates resistant to anti-TB agents in this hospital, and in particular among young patients, is alarming. Strict measures to control and prevent drug-resistant TB are urgently needed.

Survival status of veterans with lung cancer is poorer than that among civilians due to age and sex differences: a study of Chinese veterans in Taiwan.

BACKGROUND: This study was undertaken to analyze and compare the clinical characteristics and survival difference among veterans and civilians in Taiwan with lung cancer, especially non-small-cell lung cancer, and to determine whether or not veterans have a poorer prognosis than civilians. METHODS: We retrospectively reviewed the medical records and computer files of lung cancer patients diagnosed between 1996 and 2000 at our hospital. Patients' clinical characteristics, marital status, staging, treatment modality, and overall survival were analyzed and compared, based on the patients' standing as veterans or civilians. RESULTS: During this period, 3,727 lung cancer patients (2,386 veterans, 1,341 civilians) were diagnosed. The overall survival of all lung cancer patients showed that civilians had better survival than veterans (median, 12 months vs. 8 months, p < 0.001). Survival of non-small-cell lung cancer patients was also better for civilians than veterans (median, 13 months vs. 9 months, p < 0.001). Surgery was the main treatment modality in both stage I and II civilians and veterans. A greater proportion of veterans in stage II and III received radiotherapy than civilians in the same stage, with a statistically significant difference in stage III patients (p < 0.001). Multivariate survival analysis showed that age and sex were independent risk factors for mortality, while standing (veteran or civilian) was not, in both all lung cancers and non-small-cell lung cancer alone. CONCLUSION: Veterans, who mainly came from China, had a poorer prognosis than civilians when suffering from lung cancer in Taiwan, due to age and gender, rather than standing.

Adenocarcinoma of the lung presenting as a mycetoma with an air crescent sign.

An 89-year-old man was admitted to the hospital due to intermittent anterior chest wall pain for > 1 month. A chest radiograph obtained on November 9, 2004, demonstrated a mass with an irregular border, inside a thin-walled cavity, located in the superior segment of the left lower lobe. A chest CT scan revealed an irregular thin-walled cavity, 5.9 x 5.4 x 4 cm in size, with an air-crescent sign in the superior segment of the left lower lobe, and an intracavitary fungus ball-like mass. A bronchoscopic examination was performed, revealing only external compression of the left lower lobe bronchial lumen. Cultures from both the brushing cytology and brushing fungus specimens were negative. Since the patient was a heavy smoker and the chest radiograph obtained 23 months before had revealed no active pulmonary lesion, neoplastic growth was still highly suspected. Thus, an (18)F-fluoro-2-deoxyglucose positron emission tomography study was performed on November 25, and a mass with a slightly increased standard uptake value (3.17; cutoff value, 2.5) was found. He received a left lower lobe lobectomy on December 23, and a tumor with many septum-like structures connecting the surrounding pulmonary parenchymal tissue was found in the superior segment of the left lower lobe. The final pathologic diagnosis was adenocarcinoma of the lung (pT2N0M0). Thus, even though the chest radiograph and chest CT scan showed a typical air-crescent sign (ie, mass inside a cavity) favoring a mycetoma, the physician should still keep in mind that lung cancer may also unusually present in this way.

Lung cancer may develop subsequently or coincidently with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an accumulation of periodic acid-Schiff (PAS) positive lipoproteinaceous material in the alveolar space. It is usually idiopathic, and secondary to hematologic malignancy or some atypical infection. To date, there are only five published case reports of PAP occurring in association with solid organ cancer. We herein report two cases of PAP associated with lung cancer: one, a case of idiopathic PAP with subsequent development of lung cancer, and the other, a case of coexisting lung cancer and PAP. In conclusion, PAP can occur prior to or coincidently with lung cancer.

A randomized phase II study of docetaxel or vinorelbine in combination with cisplatin against inoperable, chemo-naïve non-small-cell lung cancer in Taiwan.

Cisplatin plus a third-generation anti-cancer drug, such as vinorelbine, gemcitabine, or the taxanes, are the standard regimen used in the first-line treatment of advanced non-small-cell lung cancer (NSCLC), and there is no significant difference in efficacy among the different regimens. Our aim was to evaluate the efficacy of docetaxel plus cisplatin (DC) versus vinorelbine plus cisplatin (VC) in chemo-naïve NSCLC patients. From December 2003 to May 2005, 94 patients were enrolled. The treatment dose was D 60 mg/m2 and C 60 mg/m2 intravenous infusion (IV) on day 1, or V 25 mg/m2 IV on days 1 and 8, and C 60 mg/m2 IV on day 1, every 3 weeks. In all, 209 cycles of DC and 230 cycles of VC were given to the patients in the DC (median five cycles) and VC (median five cycles) arms, respectively. There were 19 partial responses and one complete response (overall 43.5%) in the DC arm, and no complete responses, but 22 partial responses (overall 45.8%), in the VC arm. Myelosuppression was the major toxicity occurring in both arms, with grades 3 or 4 neutropenia occurring in 72.9% and 71.7% of patients, respectively. Except for alopecia (p=0.005) and diarrhea (p<0.001), which were more common in the DC arm, no significant differences in toxicity profiles were found between the two treatment arms. The median time to disease progression was 4.7 months in the DC arm and 6.3 months in the VC arm (p=0.7355). Median survival time was 13 months in the DC arm and 13.8 months in the VC arm (p=0.9656). The 1-year survival rate was 55.5% and 51.7%, respectively. After treatment, the Lung Cancer Symptom Scales showed no significant difference between the two treatment arms. We concluded that both DC and VC are appropriate regimens for use in the first-line treatment of Chinese NSCLC patients. Asthenia, one of the major side effects of docetaxel, was not a major problem in the present study. Although both regimens produced a high incidence of severe neutropenia, the majority of patients recovered rapidly without sequelae; and VC treatment is still a standard chemotherapy for Chinese NSCLC patients in Taiwan.

Serum tumor markers as predictors for survival in advanced non-small cell lung cancer patients treated with gefitinib.

BACKGROUND: Though the imaging-based response (IBR) is the most frequently used index of the therapeutic effect in cancer patients, an index based on serum tumor markers might prove to be useful, especially in patients without measurable tumors. METHODS: Paired pre- and post-treatment serum tumor markers (CEA, CA-125, and CA-199) were measured in 89 of 100 registered non-small cell lung cancer (NSCLC) patients who received gefitinib. Correlation and agreement analyses between the IBR at the 8th week and the tumor marker response (TMR) at the 4th or the 8th week were performed in patients with measurable lesions (n=68). Analysis of survival in relation to TMR was performed in all patients and in patients with no measurable lesions (n=21). RESULTS: IBR was closely correlated with individual tumor marker responses and the response of all 3 markers combined at 4 weeks (P values ranged from <0.001 to 0.002). The agreements were also significant (P values ranged from 0.001 to 0.004). In the whole group, 4-week TMR was predictive for progression-free survival (P values ranged from <0.0001 to 0.0086). In patients without measurable lesions, differences in progression-free survival and overall survival were closely correlated with the 4-week CA-125 response, CA-199 response, and TMR(overall) (P values ranged from 0.0002 to 0.0399). However, the correlation between the 8-week TMR and either IBR or survival was not significant. CONCLUSIONS: In gefitinib-treated NSCLC patients, correlation was good between 4-week TMR and IBR. Four-week TMR was predictive for survival. TMR may serve as a tool for assessing the gefitinib response in patients without measurable lesions.

A phase II study of oral vinorelbine in combination with cisplatin conducted in Taiwan in patients with unresectable localized or metastatic non-small cell lung carcinoma.

BACKGROUND: Intravenous vinorelbine plus cisplatin is widely prescribed for the treatment of NSCLC. The objective of this phase II study was to define the efficacy of an oral form of vinorelbine combined with cisplatin for first line treatment of advanced/metastatic NSCLC. PATIENTS AND METHODS: From September 2002 to December 2003, 46 chemotherapy-naive patients received 80 mg/m(2) of cisplatin on day 1 and oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: After an independent panel review, the response rate was 37.5 % [95% confidence interval (CI): 22.7-54.2%] in the evaluable population and 32.6% [95% CI: 19.5-48] in the intent-to-treat population. Median progression-free survival was 5.6 months and overall survival was 11.2 months. Grades 3 and 4 neutropenia was observed in 58.7% of patients, with febrile neutropenia and neutropenic infection in 4.3 and 8.7% of patients, respectively. The main non-haematological toxicities were hypotension, fatigue (8.7% for each) and gastrointestinal disorders with rare grades 3 and 4. CONCLUSIONS: These results suggest that the combination of cisplatin at 80 mg/m(2) on day 1 with oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks, is an active regimen, associated with acceptable toxicity. Oral vinorelbine is therefore a good alternative to the i.v. formulation.

Revisit of 1997 TNM staging system--survival analysis of 1112 lung cancer patients in Taiwan.

BACKGROUND: There is neither a nation-wide nor a large-scale, multi-institutional lung cancer database available for stage-by-stage survival analysis in Taiwan at present. METHODS: Using the data element provided by the International Association for the Study of Lung Cancer, the Taiwan Lung Cancer Society initiated a project to include native lung cancer patients into a global database. A total of 1112 Taiwan lung cancer patients treated in 7 medical centers were enrolled. RESULTS: In small cell lung cancer, patients with ipsilateral pleural effusion had a survival between those with locoregional disease alone and those with distant metastasis; however, the difference was not statistically significant (P = 0.204). In non-small cell lung cancer, tumor size had significant survival influence for patients as a whole (P < 0.001) but it did not support the further division of stage IA according to tumor size (P = 0.122). The survival was compatible in stage IIIB and IV patients and therefore, the survival impact of pleural effusion cannot be determined. In patients with pIIIA-N2 disease, those who had station 8 nodal metastasis had inferior survival (P = 0.020) and station 5 superior survival (P = 0.010). In patients with distant metastasis, bone, liver, or distant lymph node metastasis predicted an inferior survival (all P values < 0.05). CONCLUSIONS: The present study provides for comparison in this area a stage-by-stage reference for the survival of lung cancer patients. Some factors other than current TNM descriptors need to be further investigated in constructing the next version of the staging system.

Lupus erythematosus (LE) cells in ascites: initial diagnosis of systemic lupus erythematosus by cytological examination: a case report.

Systemic lupus erythematosus (SLE) is an autoimmune disease, involving multiple organs. Diverse manifestations may obscure the diagnosis and confuse our thinking process, especially when few clues are present at the beginning. Serositis is one of the various presentations, and the presence of lupus erythematosus (LE) cell in body fluid may be a hint for the final diagnosis of SLE. Herein, we present a young female patient diagnosed of SLE with initial presentation of lupus peritonitis. Finding of LE cell in ascites prompted us for immunologic survey. Diagnosis of SLE was confirmed with high titer of anti-nuclear antibody and antibody to double-stranded DNA. Cytologic examination of body fluid is mainly useful in detecting malignant cells, but high specificity of this marker aids in early diagnosis of SLE.