Imatinib Mesylate Dose Adjustment Based on Body Surface Area for CML Chronic Phase Patients Intolerant to Standard Dosage.

AIM: Chronic myelogenous leukemia (CML) chronic phase (CP) patients cannot tolerate a standard dose (400 mg/day) of imatinib mesylate (IM), sometimes needing a reduced dose. This study aimed to find convenient clinical indexes, rather than plasma trough levels of IM, to define the appropriate IM dosage. METHODS: Seventy CML CP patients who experienced an IM dose reduction, or a temporary cessation, were enrolled from 2002 to 2010. The IM treatment was resumed and maintained at either ≥400 mg in 25 patients (35.7%; group ≥400 mg) or at ≤300 mg in 45 patients (64.3%; group ≤300 mg). The various clinical characteristics of these patients were evaluated. The plasma trough level of IM was monitored in 20 patients from group ≤300 mg. RESULTS: Via multivariate analysis, the IM dosage divided by the body surface area (BSA) was an important index, presupposing a complete cytogenetic response at 12 months (CCyR12). Patients with IM/BSA >206.7 mg/m2 showed a higher probability of CCyR12 than others. The IM/BSA (221.7 mg/m2) in group ≤300 mg was higher than in group ≥400 mg (207.6 mg/m2). The sustained response and survival rate of group ≤300 mg was comparable to that of group ≥400 mg. The plasma trough level of IM was significantly correlated with the IM/BSA. CONCLUSION: Our study suggests that IM dose adjustments, based on IM/BSA, could improve the clinical outcomes in CML CP patients.

Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer.

SUMMARY: The RASSF1 gene, a putative tumor suppressor gene located on human chromosome 3p21, has attracted a great deal of attention because of frequent allelic loss and gene silencing via promoter hypermethylation in a variety of human malignancies. To evaluate the role of RASSF1A gene in lung cancer risk, genotypes of the RASSF1A promoter region (-710 C>T and -392T>C) were determined in 410 lung cancer patients and 410 normal subjects. Furthermore, to examine potential effects of the common haplotypes (C-C, T-T and C-T haplotypes) on RASSF1A transcription, luciferase reporter assays were performed in H2009 and H358 non-small cell lung cancer (NSCLC) cell lines. We found that ht2 C-T haplotype was associated with susceptibility to the risk of lung cancer in dominant (odds ratio (OR): 0.69; 95% CI: 0.46-0.99) model. In particular, we found that C-T haplotype showed a decreased risk of lung cancer in males (codominant OR: 0.59; 95% CI: 0.38-0.93 and dominant OR: 0.58; 95% CI: 0.35-0.96) and in smokers (codominant OR: 0.58; 95% CI: 0.36-0.93 and dominant OR: 0.56; 95% CI: 0.33-0.96). Interestingly, C-T haplotype induced transcriptional activity by 50-60% compared with other haplotypes in NSCLC cell lines. These results suggest that RASSF1A promoter polymorphisms affect RASSF1A expression, further contributing to the genetic susceptibility to lung cancer.

Single nucleotide polymorphisms of IGFBP-3 gene and lung cancer risk in a Korean population.

Insulin-like growth factor binding protein-3 (IGFBP-3) is a putative tumor suppressor and inhibits the mitogenic and antiapoptotic activity of insulin-like growth factor (IGF) by blocking the binding to its receptors or by IGF-independent manner. Epidemiological studies have suggested that serum level of IGFBP-3 is associated with lung cancer risk. The present study was conducted to evaluate the association between single nucleotide polymorphisms (SNPs) of the IGFBP-3 gene and susceptibility to lung cancer and the effect of the SNPs on the serum levels of IGFBP-3, total IGF-I and free IGF-I in a Korean population. After a preliminary study for polymorphism screening of the promoter region of the IGFBP-3 gene in randomly selected 41 lung cancer patients, two polymorphisms (-1590 C>A; -202 A>C) were identified with PCR-based restriction fragment length polymorphism (PCR-RFLP) and SNaPshot primer extension assay in 415 Korean lung cancer patients and 415 matched normal controls. Although the genotype and allele frequency distribution of each SNP did not differ significantly between cases and controls in the single-locus analysis, we found that the polymorphisms of -1590A and -202C were associated with increased risk for lung cancer in females (-1590 C>A; adjusted OR=2.11, 95% CI=1.08-4.12, -202 A>C; adjusted OR=1.96, 95% CI=1.02-3.75, respectively) and never-smokers (-1590 C>A; adjusted OR=2.06, 95% CI=1.12-3.78, -202 A>C; adjusted OR=1.99, 95% CI=1.10-3.62, respectively) in a dominant model after stratification for gender and smoking history. Haplotype analysis showed that carriers of A-C had significantly higher risk for lung cancer in females (dominant aOR=2.05, 95% CI=1.14-3.68) and in never-smokers (codominant aOR=1.71, 95% CI=1.11-2.64 and dominant aOR=1.99, 95% CI=1.17-3.40). Functional analysis in H1703 cell line using DNA fragments containing A-C haplotype of the promoter region showed significantly decreased transcriptional activity. Furthermore, there was a negative correlation between the number of polymorphic alleles in -1590/-202 loci and serum levels of IGFBP-3 in lung cancer patients, but it was not statistically significant in the test for linear trend. These results suggest that IGFBP-3 promoter polymorphisms of -1590 C>A and -202 A>C might be a genetic risk factor for lung cancer by means of decreased IGFBP-3 expression among females or never-smoking Koreans.

Increased serum 90K and Galectin-3 expression are associated with advanced stage and a worse prognosis in diffuse large B-cell lymphomas.

The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor metastasis has been reported, but little is known about their role in the prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL). Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in healthy controls (1,408.81 +/- 89.45 vs. 980.94 +/- 58.69 ng/ml, p = 0.036). High serum 90K (median value >or=1,249.50 ng/ml) and high galectin-3 expression (grade 3 positive staining in >75% of cells) showed a significant association with stage III/IV, >or=2 extranodal involvements and risk of high/high-intermediate international prognostic index (p < 0.05). The complete response (CR) rate (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%, 13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed CR (42.9%). The time to progression and overall survival were shorter in the group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum 90K and galectin-3 expression might be useful markers to indicate the extent of lymphoma involvement and prognosis in DLBCL.

Telomere length shortening of peripheral blood mononuclear cells in solid-cancer patients undergoing standard-dose chemotherapy might be correlated with good treatment response and neutropenia severity.

This study evaluated the telomere length changes (DeltaTL) of peripheral blood mononuclear cells before and after repetitive standard-dose nonmyeloablative chemotherapy and the association of DeltaTL with treatment response and myelosuppression severity. TL was measured with Southern blot analysis in 32 solid-cancer patients without bone marrow metastasis. The mean TL before chemotherapy (t0 TL) and after the 2nd (t1 TL), 4th (t2 TL) and 6th cycle (t3 TL) was 8.49, 8.33, 8.08 and 8.10 kb, respectively. TL became significantly decreased after 4 (p = 0.005) and 6 (p = 0.026) cycles of chemotherapy. The mean value of DeltaTL before and after completion of chemotherapy (t0 TL - t3 TL) was 0.46 kb. DeltaTL has a significant correlation with good treatment response (r = 0.448, p = 0.005) and the frequency of severe neutropenia (r = 0.417, p < 0.05). Consequently, TL of peripheral blood mononuclear cells was decreased by the repetitive nonmyeloablative standard-dose chemotherapy in solid-cancer patients without bone marrow metastasis, and DeltaTL was associated with good treatment response and neutropenia severity.

Epirubicin, cisplatin, oral UFT, and leucovorin combination chemotherapy in advanced and metastatic esophageal cancer.

BACKGROUND: The purpose of treatment in patients with advanced and metastatic esophageal cancer is to improve symptoms and maintain quality of life. Recently, the regimen including epirubicin, cisplatin, and 5-FU (ECF) has been used with protracted venous infusion (PVI), and has been reported to be an effective treatment for advanced and metastatic esophagogastric cancer. However, complications and the inconvenience associated with PVI cannot be justified for the treatment of advanced esophageal cancer. Therefore, we provided treatment with oral UFT and leucovorin instead of 5-FU PVI to improve convenience and catheter related complications. PATIENTS AND METHODS: Thirty-seven patients with advanced esophageal cancer were admitted between March 2002 and April 2005. The treatment schedule was as follows: epirubicin 50 mg/m2 iv on d 1, cisplatin 60 mg/m2 iv on d 1, oral UFT 300 mg/m2 and leucovorin 75 mg for 21 consecutive days of treatment followed by a 7-d treatment-free interval. RESULTS: The response rate was 45.9% including one complete response (95% CI: 29.8%-62%). The median survival was 13 mo (95% CI: 10-16 mo). Four patients had adenocarcinoma. Interestingly, their response rate was 75% including one complete response. Myelosuppression was the most important toxicity. Other toxicities were tolerable. CONCLUSION: The combination of epirubicin, cisplatin, UFT, and leucovorin (EPUL) could be another alternative to ECF in patients with advanced esophageal cancer. And this treatment might be more effective in adenocarcinoma of esophageal cancer.

Is noncurative gastrectomy always a beneficial strategy for stage IV gastric cancer?

PURPOSE: The purpose of this study is to suggest a treatment strategy for stage IV gastric cancer by investigating the behavioral difference between initially and recurrent metastatic disease. METHODS: We reviewed the medical records of the patients who underwent chemotherapy alone for metastatic gastric cancer between January 2006 and September 2013. Patients were divided into those who underwent chemotherapy for metastatic disease since initial diagnosis (IM group) and for metastatic recurrence after curative surgery (RM group). Survival and causes of death were compared between the 2 groups, and significant prognostic factors were also investigated. RESULTS: A total of 170 patients were enrolled in this study. Of these patients, 104 were included in the IM group and 66 in the RM group. Overall survival of the IM group did not differ from that of RM (P = 0.569). In the comparison of the causes of death, the IM group had a greater tendency to die from bleeding (P = 0.054) and pneumonia (P = 0.055). In multivariate analysis, bone metastasis (P < 0.001; HR = 2.847), carcinoma peritonei (P = 0.047; HR = 1.766), and the frequency of chemotherapy (P < 0.001; HR = 0.777) were significantly associated with overall survival of IM group. CONCLUSION: Disease-burden mainly contributes to the prognosis of metastatic gastric cancer, although noncurative gastrectomy may be helpful in reducing the mortality of initially metastatic disease. Therefore, disease-burden should be also prioritized in determining the treatment strategies for stage IV gastric cancer.

Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis. MATERIALS AND METHODS: Cytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells. RESULTS: UDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death. CONCLUSIONS: From our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.

uPAR expression under hypoxic conditions depends on iNOS modulated ERK phosphorylation in the MDA-MB-231 breast carcinoma cell line.

Urokinase plasminogen activator receptor (uPAR) plays a major role in cancer invasion and metastasis and uPAR expression is correlated with a poor prognosis in various cancer types. Moreover, the expression of uPAR is increased under hypoxic conditions. Nitric oxide (NO) and its metabolites produced by inducible nitric oxide synthase (iNOS) are important products of hypoxic stress, and NO may activate or modulate extracellular signal regulated kinase (ERK). Here, we evaluated uPA, uPAR, and activated ERK levels under hypoxic conditions, and the modulatory effects of iNOS and NO in the MDA-MB-231 human breast cancer cell line. Cells were incubated in a hypoxic or normoxic incubator and treated with PD98059 (a MEK 1/2 inhibitor, which abrogates ERK phosphorylation) and aminoguanidine (a selective iNOS inhibitor). uPAR expression, ERK phosphorylation, and uPA activity were found to be increased under hypoxic conditions. Moreover, when cells were treated with PD98059 under hypoxic conditions, uPAR was downregulated, whereas aminoguanidine markedly increased ERK phosphorylation in a dose dependent manner. Furthermore, aminoguanidine increased uPAR expression and prevented the inhibition of uPAR expression by PD98059. These results demonstrated that uPAR is induced by hypoxia and that increased uPAR expression is mediated by ERK phosphorylation, which in turn is modulated by iNOS/NO in MDA-MB-231 cells. We conclude that iNOS/NO downregulates the expression of uPAR under hypoxic conditions via ERK pathway modulation.

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. PATIENTS AND METHODS: All 53 patients received epirubicin (50 mg/m2 i.v.) on day 1 and cisplatin (60 mg/m2 i.v.) after epirubicin administration. Oral UFT 400-600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. RESULTS: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0-26.8%) with median response duration of 17.1 weeks (95% CI; 5.0-29.3 weeks, range; 7.1-51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3-31.9 weeks, range; 3.0-131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). CONCLUSION: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.

Acute arthritis of carpal bones secondary to metastatic gastric cancer.

A 39-year-old woman presented with acute onset of arthralgia in both wrists. Although her primary gastric cancer was in remission after previous treatment, carcinomatous arthritis was suggested by the osteolytic radiographic findings and refractoriness to nonsteroidal anti-inflammatory drugs, which was then confirmed by synovial fluid cytopathology. In view of the high incidence of gastric cancer in Korea, gastric cancer involving the carpal bones should be considered when we encounter a patient presenting with inflammatory peripheral joint arthritis, which might be the first sign of recurrence.

Incidence of anemia in older Koreans: community-based cohort study.

Most epidemiologic data are related to the prevalence of anemia, and there is little information regarding the incidence or etiology of newly diagnosed anemia in older people. The purpose of this study was to define the incidence and characteristics of anemia in the elderly population of Korea. Three hundred thirty-two independent, community-living, elderly persons aged 60 years and older were enrolled, and laboratory tests including iron profiles were performed. The mean age was 72+/-4.8 years and the mean hemoglobin was 13.4+/-1.1g/dl. During the follow-up period of 3 years, 24 subjects (3 males and 21 females) were newly diagnosed with anemia, which led to a 3-year incidence of 7.2% (24/332). Among the 24 subjects with new-onset anemia, iron deficiency anemia (IDA) was diagnosed in 5 subjects, while anemia of chronic disease (ACD) was detected in 8 subjects. Underlying illnesses were diabetes mellitus, osteoarthritis, renal insufficiency, hypothyroidism and malignancy. In those subjects with new-onset anemia, the serum iron, ferritin, transferrin saturation and albumin were lower than in the normal group. In conclusion, the 3-year incidence of anemia among Korean elderly people was determined to be 7.2%, and ACD was the most commonly defined cause of anemia.

Influence of socioeconomic status on survival and clinical outcomes in patients with advanced gastric cancer after chemotherapy.

BACKGROUND: Socioeconomic inequalities are known to influence the survival of cancer patients due to differences in treatment modalities and disease extent at diagnosis. However, there are few studies regarding the influence of socioeconomic status on patient survival, especially after palliative chemotherapy for advanced gastric cancer. PATIENTS AND METHODS: This retrospective study was performed on 138 advanced gastric cancer patients who received palliative chemotherapy. Demographic, socioeconomic, and cancer-related variables were analyzed according to education level. Effects of socioeconomic factors and cancer-related variables on patient survival were also evaluated. RESULTS: In our study, higher education level (> 6 years of schooling; p = 0.01), disease control (p < 0.01), and a greater number of chemotherapeutic agents (≥ 5 drugs; p < 0.01) were associated with a significant increase in median survival. Multivariate analysis showed that a higher education level (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.35-0.82; p < 0.01), disease control (HR 0.21; 95% CI 0.13-0.34), and total number of chemotherapeutic agents used (HR 0.44; 95% CI 0.26-0.73) were significantly associated with prolonged survival. CONCLUSIONS: Among socioeconomic factors, only higher education level was associated with better survival. Increase in survival was also associated with clinical outcomes, including total number of chemotherapeutic agents used and disease control after chemotherapy.

Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment.

PURPOSE: There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC. MATERIALS AND METHODS: We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy. RESULTS: The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death. CONCLUSION: Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

Combination of gemcitabine and carboplatin as first line treatment in elderly patients or those unfit for cisplatin-based chemotherapy with advanced transitional cell carcinoma of the urinary tract.

PURPOSE: Although cisplatin-based chemotherapy is the standard of care for advanced transitional cell carcinoma, tolerability is a challenging issue in unfit patients. This study was conducted to evaluate the efficacy, toxicity, and tolerability of the combination of gemcitabine and carboplatin in unfit patients with advanced transitional cell carcinoma. METHODS: Thirty-one patients who had advanced transitional cell carcinoma and one of the following clinical features were evaluated: Eastern Cooperative Oncology Group performance status equal or greater than 2, age older the 75 years or estimated glomerular filtration rate less than 60 ml/min. The patients were treated with carboplatin and gemcitabine delivered every 4 weeks. RESULTS: Of the 31 patients, 71 % had an estimated glomerular filtration rate of less than 60 ml/min, and the remaining patients were treated by this protocol due to poor performance status or age older than 75. The median age of the patients was 74 years old. A total of 162 cycles of treatment were delivered to the patients. The overall response rate was 45.1 %. After the median follow-up of 15 months, the median progression-free survival time was 9.4 months (95 % CI 7.3-11.4) and overall survival time was 20 months (95 % CI 14.9-25.0). Grades 3 and 4 anemia, thrombocytopenia, and neutropenia were observed in 22.6, 6.45, and 6.45 % of patients, respectively. There was no treatment-related mortality in our patient series. CONCLUSION: The combination of gemcitabine and carboplatin is effective in elderly patients with advanced transitional cell carcinoma or those unfit for cisplatin-based chemotherapy, with manageable toxicity.

The relationship between Helicobacter pylori infection and the effects of chemotherapy in patients with advanced or metastatic gastric cancer.

PURPOSE: Several reports have shown a better prognosis in gastric cancer patients who are positive for Helicobacter pylori (HP) infection compared with negative cases. However, there are currently no studies that investigate the relationship between HP infection and the effects of chemotherapy in gastric cancer patients. In this study, we report the relationship between HP infection and chemotherapy effects in patients with advanced or metastatic gastric cancer. METHODS: Sixty-one patients with advanced or metastatic gastric cancer were enrolled in this study. Biopsies were conducted around the tumor site to determine HP status. Patients were then treated with combination 5-FU and cisplatin-based chemotherapy. And we compared chemotherapy response rate and overall survival rate between HP infection group and without HP infection group. RESULTS: Twelve of 18 patients with HP infection (66.7 %) and 9 of 42 patients without HP infection (21.4 %) showed a partial response to chemotherapy (Chi square P = 0.001). Patients with HP infection had a median survival time of 13 months (95 % CI, 6.9-19.1 months), which was significantly longer than that of patients without HP infection (9 months; P = 0.027, log-rank test). CONCLUSIONS: Patients with advanced or metastatic gastric cancer with concomitant HP infection had a better response to chemotherapy and had an improved overall prognosis compared with patients without HP infection. Further studies are warranted to confirm these findings.

Treatment results including more than third-line chemotherapy for patients with advanced non-small cell lung cancer.

Recently, third-line chemotherapy for advanced non-small cell lung cancer (NSCLC) was accepted as a reasonable therapeutic option in patients with a favorable performance status. In practice, however, palliative chemotherapy has been performed for patients with a favorable performance status, even after third-line chemotherapy. Although multiple cycles of palliative chemotherapy were performed for these patients, there are little data of observation for courses of treatment from first-line to the last chemotherapy. We reviewed the courses of treatment for 82 patients with advanced NSCLC that had been admitted for platinum-based chemotherapy as a first-line treatment. Additional cycles of palliative chemotherapy were provided as monotherapy, based on the attending physician's decision considering patient performance status and toxicity after disease progression for previous chemotherapy. The median number of chemotherapy lines and cycles were 2 and 7, respectively, from first-line to the last chemotherapy. The median overall survival was 24 months in the response group of first-line chemotherapy, compared to 15 months for the entire study group. In the response group, the median number of chemotherapy cycles was 15 and patients received a median of 3 lines of chemotherapy. A total of 33 patients were candidate third-line chemotherapy or more. The median survival was 23 months for patients treated with more than third-line chemotherapy, compared to 7 months for patients treated with less than second-line chemotherapy. We conclude that long-standing chemotherapy is not beneficial to all NSCLC patients. However, patients with a favorable response to first-line chemotherapy tend to receive a higher number and more cycles of chemotherapy than the non-response group. Furthermore, multi-line chemotherapy appears to increase survival in the response group. Further studies will be needed to confirm these results.