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Bladder cancer (BC) is the most frequently occurring cancer of the urinary system, with non-muscle-invasive bladder cancer (NMIBC) accounting for 75–85% of all the bladder cancers. Patients with NMIBC have a good survival rate but are at high risk for tumor recurrence and disease progression. Intravesical instillation of antitumor agents is the standard treatment for NMIBC following transurethral resection of bladder tumors. Chemotherapeutic drugs are broadly employed for bladder cancer treatment, but have limited efficacy due to chemo-resistance and systemic toxicity. Additionally, the periodic voiding of bladder and low permeability of the bladder urothelium impair the retention of drugs, resulting in a weak antitumoral response. Chitosan is a non-toxic and biocompatible polymer which enables better penetration of specific drugs to the deeper cell layers of the bladder as a consequence of temporarily abolishing the barrier function of urothelium, thus offering multifaceted biomedical applications in urinary bladder epithelial. Nowadays, the rapid development of nanoparticles significantly improves the tumor therapy with enhanced drug transport. This review presents an overview on the state of chitosan-based nanoparticles in the field of intravesical bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Cancer is known as a second major cause of death globally. Nowadays, several modalities have been developed for the treatment of cancer. Radiotherapy and chemotherapy are the most common modalities in most countries. However, newer modalities such as immunotherapy and targeted therapy drugs can kill cancer cells with minimal side effects. All anticancer agents work based on the killing of cancer cells. Numerous studies are ongoing to kill cancer cells more effectively without increasing side effects to normal tissues. The combination modalities with low toxic agents are interesting for this aim. Curcumin is one of the most common herbal agents that has shown several anticancer properties. It can regulate immune system responses against cancer. Furthermore, curcumin has been shown to potentiate cell death signalling pathways and attenuate survival signalling pathways in cancer cells. The knowledge of how curcumin induces cell death in cancers can improve therapeutic efficiency. In this review, the regulatory effects of curcumin on different cell death mechanisms and their signalling pathways will be discussed. Furthermore, we explain how curcumin may potentiate the anticancer effects of other drugs or radiotherapy through modulation of apoptosis, mitotic catastrophe, senescence, autophagy and ferroptosis. [ABSTRACT FROM AUTHOR]

Summary Background Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. Methods Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR -activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma. Patients took 20–240 mg osimertinib per day until disease progression or development of intolerable side-effects. Plasma samples were collected every 6 weeks and tumour tissue biopsy was done at study entry and was optional after disease progression. We tested samples for resistance mechanisms, including EGFR -activating, Thr790Met, and Cys797Ser mutations, and assessed associations with overall survival, progression-free survival, and survival after disease progression. Findings Of 71 patients enrolled in AURA, 53 were eligible for this analysis. Median progression-free survival was 11·1 months (95% CI 8·4–13·9) and overall survival was 16·9 months (11·7–29·1). 47 patients had disease progression. Median overall survival after osimertinib progression was 5·4 months (95% CI 4·1–10·0). Plasma samples were available for 40 patients after disease progression. 12 (30%) of these had the Thr790Met mutation (four of whom also had Cys797Ser mutations). Patients without detectable EGFR -activating mutations in plasma before treatment had the best overall and post-progression survival (22·4 months, 95% CI 15·6–not reached, and 10·8 months, 7·2–not reached, respectively). Loss of the Thr790Met mutation but presence of EGFR -activating mutations in plasma were associated with the shortest progression-free survival (median 2·6 months, 95% CI 1·3–not reached). In 22 post-progression tumour samples, we found one squamous cell and two small-cell transformations. We detected Thr790Met in nine (50%) of 18 samples, Cys797Ser in two (17%) of 12, cMET amplification in five (50%) of ten, BRAF mutation in one (8%) of 13, and KRAS mutation in one (8%) of 13. Interpretation Heterogeneous resistance mechanisms developed in patients receiving osimertinib. Differences in resistance mechanisms might dictate future development strategies for osimertinib in clinical trials. Funding AstraZeneca, Taiwan Ministry of Science and Technology. [ABSTRACT FROM AUTHOR]

Among treatment modalities for lung cancer, the most promising therapy is the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Both erlotinib and gefitinib, the two first-generation EGFR-TKIs, exhibit significant clinical responses for patients with lung adenocarcinoma. However, few studies have compared the effects of these two drugs, and results have been inconclusive because of the small sample sizes in these studies. Therefore, this study was conducted to investigate this issue. This retrospective nationwide cohort study enrolled NSCLC patients who received EGFR-TKIs after previous chemotherapy in Taiwan between 1996 and 2010 from the National Health Insurance Research Database. Clinical response and survival after receiving erlotinib and gefitinib were compared using logistic and Cox regression analyses, respectively. Inverse propensity score weighting and a sensitivity analysis in the EGFR-TKI responder (clinical improvement by taking EGFR-TKIs for 90 days), adherent patients (receiving EGFR-TKI on a daily basis), adenocarcinoma, and adenocarcinoma with second-line TKIs subgroup were performed for bias adjustment. A total of 7222 patients, including 4592 (63.6%) who received gefitinib, were identified. In the survival analysis, erlotinib was associated with a decline in 1-year progression-free survival (PFS) (hazard ratio, HR: 1.15 [1.09-1.21]) and overall survival (OS) (HR: 1.10 [1.03-1.18]). The effects of various TKIs were consistent in the 4939 EGFR-TKI responders, adherent subgroup, adenocarcinoma subgroup, and adenocarcinoma with second-line TKIs subgroup. In previously treated EGFT-TKI-naive NSCLC patients, those receiving gefitinib exhibited a longer PFS and OS than those receiving erlotinib. Additional large-scale randomized controlled trials are warranted to confirm this finding. [ABSTRACT FROM AUTHOR]

Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN) which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2) and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM) were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer. [ABSTRACT FROM AUTHOR]

Background/purpose: Meningeal carcinomatosis (MC) is a rare neurologic complication of lung cancer. Occasionally, it is the initial presentation of lung cancer. The clinical features of MC exclusively in lung cancer patients have not been well identified and characterized. The purpose of this report is to disclose the clinical features, laboratory findings, treatment and survival of patients with MC from lung cancer.Methods: We reviewed the medical records of 34 lung cancer patients with cytologically diagnosed MC at National Taiwan University Hospital from 1992 to 2002. Clinical symptoms and signs, cerebrospinal fluid parameters and lung cancer staging at the time of presentation were summarized. Previous treatment modalities for lung cancer, various treatments and response of MC, complications and survival times were also analyzed.Results: Cerebrospinal fluid cytology revealed adenocarcinoma in 32 patients, and small cell carcinoma and squamous cell carcinoma in one each. MC occurred in approximately 0.7% of lung cancer patients. Nine patients had MC as the initial presentation of lung cancer. Symptom improvement was found in six patients who had whole brain irradiation for MC and one patient who had a ventriculoperitoneal shunt. Two of the patients with whole brain irradiation survived for longer than 1 year. Survival from cytologic diagnosis of MC ranged from 1 day to 82 weeks (median, 5.1 weeks). There was no difference in survival between patients treated by whole brain irradiation and other treatment modalities.Conclusion: The prognosis of MC from lung cancer is poor. A prospective study is needed to establish the effectiveness of combined modality therapy for patients with MC from lung cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] The combination of chemotherapy (CT) and chemodynamic therapy (CDT) is an emerging therapeutic strategy for tumors; however, its therapeutic efficacy is usually impaired by the shortage of high-efficiency intracellular catalysts for CDT and the poor tumor selectivity of CT. To address this concern, novel carrier-free nanodrugs (CMC-DD2) self-assembled from the natural melanin complex (CMC) with a superior CDT performance, and dehydroabietic acid hexamer (DD2) displaying a potent antitumor activity were proposed for the synergistic combination of CT and CDT. CMC-DD2 preferred to enter tumor cells and localize in the nucleus after lysosome escape due to its pH-dependent charge-reversal properties. Nanodrugs internalized by the nucleus directly bound the DNA and altered its conformation. Then, the dissociation of CMC-DD2 was efficiently triggered by intracellular hydrogen peroxide (H 2 O 2) with the release of DNA damaging agents, including nitrate anions, hydroxyl radicals (●OH) and DD2. Finally, severe DNA damage induced mitochondrial apoptosis in HepG2 cells. An in vivo assessment further demonstrated the superior tumor selectivity and suppressor capacity and no/low toxicity of the nanodrugs. Overall, novel carrier-free, charge-reversal, nucleus-targeting, biodegradable, and DNA-affinity nanodrugs represent safe and effective platforms for the combination of CT and CDT. [ABSTRACT FROM AUTHOR]

Summary: This study was designed to compare the outcome of stage IIIB/IV non-small cell lung cancer patients who were treated with chemotherapy but did not participate in clinical trials of first-line chemotherapy with patients that had been treated with three clinical trials during this period. From October 1997 through October 1999, 132 patients (stage IIIB, 31 patients; stage IV, 101 patients) who received at least one dose of chemotherapy but did not participate in first-line chemotherapy trials were included. Response was evaluated in 132 patients. Six (4.5%) achieved a complete response and 32 (24.3%) achieved a partial response, resulting in an overall response rate of 28.8% (95% CI, 21.0–36.6). The median overall survival for all 132 patients was 11 months (95% CI, 9.5–12.5), and the median progression-free survival was 4.2 months (95% CI, 3.4–5.0). The median overall and progression-free survival for patients (N =129) who participated in one of three clinical trials during the study period was 13.5 months (95% CI, 11.2–15.8) and 5.6 months (95% CI, 4.9–6.0), respectively. There was no significant difference in overall and progression-free survival between patients who did or did not participate in clinical trials (overall survival: P =0.36; progression-free survival: P =0.57). Our data suggest that the survival of patients who received chemotherapy but did not participate in clinical trials was similar to patients participated in clinical trials. [Copyright &y& Elsevier]

Purpose The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). Methods and materials From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded. Radiographic response was assessed. Brain progression-free survival (BPFS) and overall survival were calculated and outcome prognostic factors were evaluated. Results Median follow-up time was 13.5 months. Of the EGFR-genotyped patients, 79 (65%) were EGFR mutants, and 42 (35%) were wild type. Presence of EGFR mutations was associated with higher radiographic complete response rates (CRR). Median time to develop new BM after SRS was significantly longer for mutant-EGFR patients (17 versus 10.5 months, p  = 0.02), predominantly for those with adjuvant TKI therapy (26.3 versus 15 months, p  = 0.01). EGFR mutations independently predicted better BPFS (HR = 0.55, p  = 0.048) in multivariate analysis. Conclusions In patients with NSCLC treated with SRS for BM, the presence of EGFR mutations is associated with a higher CRR, longer time for distant brain control, and better BPFS. The combination of SRS and TKI in selective patient group can be an effective treatment choice for BM with favorable brain control and little neurotoxicity. [ABSTRACT FROM AUTHOR]

Objectives The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight. Materials and methods This multicenter, randomized, placebo-controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas ® test, KRAS mutation by cobas ® KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate. Results Overall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations ( p < 0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR = 0.32, 95% confidence intervals [CI]: 0.14–0.69, p = 0.0024). Conclusion Activating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation. [ABSTRACT FROM AUTHOR]

Objective Previous studies have indicated that EGFR exon 19 deletions in non-small cell lung cancer (NSCLC) are associated with better outcomes to tyrosine kinase inhibitors (TKIs) than the L858R mutation. This study aimed to evaluate whether T790M, a resistant mutation, is more likely to coexist with L858R mutation than with exon 19 deletions in pretreatment NSCLC patients. Materials and method We searched MEDLINE and EMBASE up to Nov 30th, 2015 to identify randomized controlled trials (RCTs) and observational studies that reported pretreatment T790M and EGFR-activating mutation. A meta-analysis was performed using a random-effects model. The primary outcome was odds ratio (OR) of pretreatment T790M mutation in NSCLC co-existing with L858R mutation and exon 19 deletions. Stratified analysis was performed based on sensitivity of mutation detection methods for T790M. Results We identified 15 observational studies and 3 RCTs for analysis. Pretreatment T790M was more frequent in L858R than in exon 19 mutated patients. The association of T790M and L858R was statistically significant in observational studies (OR, 1.65, 95% CI, 1.17–2.32), with less precision in RCTs (OR, 1.84, 95% CI, 0.96–3.52). In the stratified analysis based on the sensitivity of the mutation detection methods, the association was observed in the studies using intermediately (detection limit <5% and ≥0.1%; OR, 2.23, 95% CI, 1.19–4.17) and highly sensitive methods (detection limit <0.1%; OR, 1.74, 95% CI, 1.10–2.73), but not in those using low sensitivity methods (detection limit >5%; OR, 1.28, 95% CI, 0.74–2.23). Conclusions Pretreatment EGFR T790M mutation is more likely to coexist with L858R mutation than with exon 19 deletions in NSCLC. This association was observed only in studies using sensitive mutation detection methods (<5%). [ABSTRACT FROM AUTHOR]

Summary: Background: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m2 on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m2 on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15–28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779. Findings: From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2–8·3], vs 6·0 months [5·6–7·1], hazard ratio [HR] 0·57 [0·47–0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3–20·8) and 15·2 months (12·7–17·5), respectively (HR 0·79 [0·64–0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9–20·4] vs 6·9 months [5·3–7·6], HR 0·25 [0·16–0·39]; p<0·0001; median overall survival 31·4 months [22·2–undefined], vs 20·6 months [14·2–26·9], HR 0·48 [0·27–0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). Interpretation: Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. Funding: F Hoffmann-La Roche. [ABSTRACT FROM AUTHOR]

Abstract: Thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are target enzymes of inhibition by pemetrexed, an antifolate for treatment of advanced non-small-cell lung cancer (NSCLC). This study is to evaluate the association of TS and DHFR expressions and the treatment efficacy of pemetrexed in NSCLC patients. From January 2006 to October 2008, patients with advanced NSCLC treated with pemetrexed after prior chemotherapy were included. The TS and DHFR expressions in tumor tissues were examined by immunohistochemistry and evaluated by a semiquantitative histologic score (H-score). The H-score was derived from the degrees of intensity of tumor cells multiplied by the percentage of positive neoplastic cells. The medical records were reviewed and analyzed with respect to patients’ characteristics, histology types, treatment responses and survivals. Among 268 NSCLC patients treated with pemetrexed, 49 had tumor specimens available for TS and DHFR evaluation. The TS expression was positively correlated with DHFR expression (r 2 =0.11, p =0.02). Patients with low TS (≤150) expression had a longer median progression-free survival (PFS) than those with high TS (>150) expression (4.8 vs. 3.4months; p =0.01). Patients with low DHFR expression (≤120) also had a longer median PFS than patients with high DHFR expression (>120), which was not statistically significant (5.8 vs. 3.6months; p =0.33). In patients with adenocarcinoma, the low TS patient group also had a longer median PFS and a longer median overall survival (OS) as compared with patients with high TS expression (PFS, 4.8 vs. 3.8months, p =0.03; OS, 21.4 vs. 10.0months, p =0.03). Nevertheless, the association of DHFR expression level and median PFS as well as OS were not statistically significant. TS expression, rather than DHFR, may be an important predictive factor for treatment efficacy of pemetrexed in NSCLC patients. [Copyright &y& Elsevier]

Summary: Background: Epirubicin was effective for the treatment of non-small cell lung carcinoma (NSCLC). This study compared the efficacy and safety of gemcitabine plus conventional-dose epirubicin (GE) with gemcitabine–cisplatin (GC) as first-line chemotherapy for stage IIIB/IV NSCLC and evaluated the predictive value of nuclear expression of excision repair cross-complementing group 1 (ERCC1) and topoisomerase IIα (TopoIIα) on treatment outcome. Patients and methods: Patients were randomized to GE (gemcitabine, 1000mg/m2 on days 1, 8, and 15 and epirubicin, 70mg/m2 on day 15) or GC (gemcitabine, 1000mg/m2 on days 1, 8, and 15 and cisplatin, 80mg/m2 on day 15). Treatment cycles were repeated every 4 weeks. Immunohistochemical study of ERCC1 and TopoIIα was done for patients with available tumor specimens. Results: The response rate was 31.0% (95% CI 16.4–45.5%) for GC (n =41) and 37.2.0% (95% CI 22.2–52.3%) for GE (n =39). No significant differences in median time-to-treatment-failure (TTF) (GC, 6.1 months; GE, 6.2 months) or overall survival (GC, 13.2 months; GE, 21.5 months) were found between the two arms. Grade 3/4 neutropenia and febrile neutropenia were more common in GE. However, delay of protocol treatment due to leukopenia was similar between the two arms. Patients with expression of both ERCC1 and TopoIIα had a significantly shorter TTF (median 2.4 months, 95% CI 0.7–4.1 months) than other patients (median 8.8 months, 95% CI 5.8–11.8 months) (p =0.04). Conclusion: GE regimen is effective and well-tolerated for NSCLC patients. Expression of both ERCC1 and TopoIIα may be associated with poor response to chemotherapy. [Copyright &y& Elsevier]

Summary: 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. [Copyright &y& Elsevier]