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| 2. |
- Hermes, Andreas, et al.
(författare)
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Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial.
- 2008
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 26:26, s. 4261-7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: A Japanese randomized trial showed superior survival for patients with extensive-disease (ED) small-cell lung cancer (SCLC) receiving irinotecan plus cisplatin compared with etoposide plus cisplatin. The present trial evaluated the efficacy of irinotecan plus carboplatin (IC) compared with oral etoposide plus carboplatin (EC). PATIENTS AND METHODS: Patients with ED SCLC were randomly assigned to receive either IC, which consisted of carboplatin (area under the curve = 4; Chatelut formula) and irinotecan (175 mg/m2) intravenously both on day 1, or EC, which consisted of carboplatin as in IC and etoposide (120 mg/m(2)/d) orally on days 1 through 5. Courses were repeated every 3 weeks with four cycles planned. Doses were reduced by one third in patients with a WHO performance status (PS) of 3 to 4 and/or age older than 70 years. Primary end point was overall survival (OS). Secondary end points were quality of life (QOL) and complete response (CR) rate. RESULTS: Of 220 randomly assigned patients, 209 were eligible for analysis (IC, n = 105; EC, n = 104). Thirty-five percent were older than 70 years, and 47% had a PS of 2 to 4. The groups were well balanced with respect to prognostic factors. OS was inferior in the EC group (hazard ratio = 1.41; 95% CI, 1.06 to 1.87; P = .02). Median survival time was 8.5 months for IC compared with 7.1 months for EC. One-year survival rate was 34% for IC and 24% for EC. CR was seen in 18 IC patients compared with seven EC patients (P = .02). There were no statistically significant differences in hematologic grade 3 or 4 toxicity. Grade 3 or 4 diarrhea was more common in the IC group. QOL differences were small, with a trend toward prolonged palliation with the IC regimen. CONCLUSION: IC prolongs survival in ED SCLC with slightly better scores for QOL.
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- Bergqvist, Michael, et al.
(författare)
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Role of non-taxane-containing chemotherapy in advanced non-small cell lung cancer
- 2006
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Ingår i: American Journal of Cancer. - : Springer Science and Business Media LLC. - 1175-6357 .- 2230-6064. ; 5:4, s. 223-244
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Tidskriftsartikel (refereegranskat)abstract
- Treatment for advanced-stage NSCLC generally includes the use of systemic chemotherapy as well as biologic therapies (targeted therapy) at later stages of the disease. However, in general, NSCLC is moderately sensitive to the currently available cytotoxic drugs, so the intention of chemotherapeutic treatment in the advanced setting is mainly palliative. Several treatment regimens are available, but in the first-line setting, treatment traditions differ both within countries and between various parts of the world. The role of taxaneplatinum chemotherapeutic combinations (mainly used in North America) has been questioned in the palliative setting since these combinations are known to cause neutropenia, skin and nail problems, as well as neurological toxicity. This review aims to summarize the current knowledge about the role of non-taxane therapy for patients with advanced NSCLC, with a focus on gemcitabine, vinorelbine, etoposide, pemetrexed, irinotecan, epidermal growth factor receptor (EGFR)-inhibiting agents, angiogenesis inhibitors, and small molecules. The compilation of literature in the present review indicates that the use of non-taxane treatment for patients with advanced NSCLC has an anti-tumor effect that is not different from that which can be seen with various taxane combinations. Furthermore, the combination of cisplatin with gemcitabine or vinorelbine seems to be a most compelling regimen in the first-line setting because of its modest toxicity (when administered by experienced staff), favorable clinical response, and relatively low drug cost. It is also clear that the novel therapies (EGFR inhibitors and inhibitors of angiogenesis) that have been approved so far will be of great clinical value, however, their use will be restricted to small, well defined, subpopulations of patients. The great challenge now is to define the populations benefiting from these novel therapies. © 2006 Adis Data Information BV. All rights reserved.
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- Cullen, MH, et al.
(författare)
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A Randomized phase III trial comparing standard and high-dose pemetrexed as second-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer
- 2008
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 939-945
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Tidskriftsartikel (refereegranskat)abstract
- Background: This phase III randomized trial compared pemetrexed 500 mg/m2 (P500) with pemetrexed 900 mg/m2 (P900) to determine whether higher dosing benefits non-small-cell lung cancer (NSCLC) patients as second-line therapy. Patients and methods: Patients with locally advanced or metastatic NSCLC, previously treated with platinum-based chemotherapy, were randomly assigned to receive i.v. P500 or P900 every 3 week. Results: Accrual was terminated with 588/600 patients enrolled because an interim analysis indicated a low probability of improved survival and numerically greater toxicity on the P900 arm. P900 patients were permitted to continue treatment at P500. No statistical difference was observed between the treatment arms (P500 versus P900) for median survival {6.7 versus 6.9 months, hazard ratio [HR] = 1.0132 [95% confidence interval (CI) 0.837-1.226]}, progression-free survival [2.6 versus 2.8 months, HR = 0.9681 (95% CI 0.817-1.147)], or best overall tumor response [7.1% versus 4.3% (P = 0.1616)]. The incidence of drug-related grade 3/4 toxicity was typically <5% on both treatment arms, but was numerically higher on the P900 arm for most toxicity categories. Conclusions: P900 did not improve any efficacy measure over P500. P500 i.v. every 3 week remains the standard pemetrexed dose for second-line treatment of platinum-pretreated advanced NSCLC.
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- Hasmats, Johanna, et al.
(författare)
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Using whole exome sequencing to identify genetic candidates for carboplatin and gemcitabine induced toxicities
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Chemotherapies are associated with significant inter-individual variability in therapeutic effect and adverse drug reactions. In lung cancer the use of gemcitabine and carboplatin induces grade 3-4 myelosuppression in about ¼ of the patients while an equal fraction of patients are basically unaffected in terms of myelosuppressive side effects. We therefore set out to try to identify genetic markers for gemcitabine / carboplatin induced myelosuppression. We selected 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0-1 after the first chemotherapy cycle) by the chemotherapy out of 243 lung cancer patients treated with gemcitabine / carboplatin. These patients were exome sequenced and their genetic differences compared using six different bioinformatic strategies; whole exome non-synonymous SNV association analysis, deviation from Hardy-Weinberg equilibrium, analysis of genes selected by a priori biological knowledge, analysis of genes selected from gene expression meta-analysis of toxicity data sets, Ingenuity pathway analysis and FunCoup network enrichment analysis. All patients were successfully sequenced and 5000-7000 non-synonymous single nucleotide variants were identified in each patient. PI3 (elastase specific inhibitor in neutrophils) showed the strongest association in the single SNV analysis (nominal p=0.0005). Further, variants within IL37, an inhibitor of the innate immune system, and CSAG1, a tumor antigen, differed among the two patient groups and appeared among the top hits in several of the performed analysis, indicating that the approach identifies genetic variants associated with the immune system and tumor differentiation, which might be important for the sensitivity to chemotherapeutic agents. However, the associations reported here are in a need of replication before clinical interpretations can be made.
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| 9. |
- Koch, Andrea
(författare)
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Clinical Aspects of Inflammation in Non-small Cell Lung Cancer
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lung cancer is the most common cause of cancer death worldwide, with about 1.2 million deaths every year. In Sweden, about 3500 new cases are diagnosed every year. The majority of patients presents with advanced non-small cell lung cancer (NSCLC) and is treated with palliative intent. Standard treatment in these patients in performance status 0-2 is combination chemotherapy. Radiotherapy may be added for palliative purposes. Median survival time with such treatment is 6-10 months. New treatment strategies are urgently needed. There is growing evidence for a link between cancer and inflammation and consequently, inflammation may be a possible target for the treatment of lung cancer.The aim of this thesis was to study clinical aspects of inflammation in non-small cell lung cancer. A central issue was to adapt the projects as close to clinical routine as possible.In a retrospective study of 289 patients (paper I), we investigated the prognostic value of Creactive protein (CRP), a nonspecific marker of systemic inflammation, and smoking in patients with advanced NSCLC treated with palliative first-line chemotherapy. We found that patients with elevated CRP values (≥10 mg/ml) and current smokers at onset of treatment had inferior survival compared to patients with normal CRP values and patients who were not smoking. CRP and smoking status were independent prognostic factors and provided additional information to established prognostic factors such as stage of disease and performance status.The expression of COX-2, an important enzyme involved in inflammation, was prospectively analysed in 53 patients with cytologically diagnosed lung cancer (paper II). The study showed that the analysis of COX-2 expression in cytological material is technically easy to perform with routine diagnostic methods and results in good quality slides. There was great variation in the proportion of COX-2 positive cells between the patients as well as in the intensity of staining between individual cells in many single cases.The major project (paper III) of this thesis was the CYCLUS study, an academic, randomised, double-blind, phase III trial. The scientific question was if addition of the COX-2 inhibitor celecoxib to first-line palliative chemotherapy would prolong survival in patients with advanced NSCLC. 316 patients were included at 13 centres in Sweden. There was no survival difference between the treatment arms. Celecoxib appeared to have more favourable effect on survival in women than in men, but the differences were not significant. Small but not statistically significant differences in global quality of life and pain were seen favouring the celecoxib group. No increased incidence of cardiovascular events was observed in the celecoxib group.
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| 10. |
- Koch, Andrea, et al.
(författare)
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Cyclooxygenase-2 expression in lung cancer cells evaluated by immunocytochemistry
- 2011
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Ingår i: Diagnostic Cytopathology. - : John Wiley and Sons. - 8755-1039 .- 1097-0339. ; 39:3, s. 188-193
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Tidskriftsartikel (refereegranskat)abstract
- Cyclooxygenase-2 (COX-2) expression may be a prognostic factor in lung cancer. In previous studies, COX-2 expression has almost exclusively been evaluated with immunohistochemical methods performed on histology sections of tissue biopsies. However, in clinical practice, lung cancer is often diagnosed with cytological techniques only. We present methodology and results from analysis of COX-2 expression with immunochemistry on cytological material in 53 patients with lung cancer. Preparation and staining with the method established at our laboratory were easy to perform and resulted in good quality slides. The percentage COX-2-stained cells and the intensity of staining varied widely between and within the different cases. The proportion of positively stained tumor cells was as follows: <1% in 20 patients, 1-10% in 7 patients, 11-50% in 17 patients, and more than 50% in 9 patients. In 17 cases, groups of cells with different intensity of COX-2 staining were found in the same slide. In conclusion, immunocytochemical analysis of COX-2 expression is technically easy to perform with routine diagnostic procedures. There is a great variation in the proportion of COX-2-positive cells among patients and in the intensity of staining among individual cells in many single cases. Diagn. Cytopathol.2011;39:188-193. © 2010 Wiley-Liss, Inc.
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