Phase II trial of raltitrexed ('Tomudex') in advanced small-cell lung cancer.

Raltitrexed, a thymidylate synthase inhibitor, was given to 21 patients with advanced small-cell lung cancer, at a dose of 3 mg m(-2) as a 15-min intravenous infusion at 21-day intervals. All of the patients had extensive disease and 17 had received prior therapy. Patients with disease refractory to primary chemotherapy were excluded. Forty-one treatment cycles were given (median two, range one to four). The drug was well tolerated. No objective tumour response was documented. The patients had chemoresistant disease, as shown by a response in only one of ten patients who went on to receive alternative cytotoxic regimens. We conclude that raltitrexed given in this schedule is inactive as second line therapy for small-cell lung cancer

Single-agent gemcitabine versus cisplatin-etoposide: Early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer

Background This randomised study was designed to determine the response rate, survival and toxicity of single-agent gemcitabine and cisplatin-etoposide in chemo-naïve patients with locally advanced or metastatic non-small-cell lung cancer. Patients and methods Gemcitabine 1,000 mg/m2 was given as a 30 min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 (following cisplatin), 2 and 3. Major eligibility criteria included histologically confirmed non-small-cell lung cancer, measurable disease, Zubrod PS 0-2; no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. Results 146 patients were enrolled, 71 patients on gemcitabine and 75 patients on cisplatin-etoposide. Patient characteristics were well matched across both arms. Sixty-six gemcitabine patients and 72 cisplatin-etoposide patients were evaluable. Partial responses were seen in 12 gemcitabine patients (18.2%; 95% CI: 9.8-30) and 11 cisplatin-etoposide patients (15.3%; 95% CI: 7.9-25.7). Early indications show no statistical differences between the two treatments with respect to time to disease progression or survival. Haematological and laboratory toxicity were moderate and manageable. However, hospitalisation because of neutropenic fever was required for 6 (8%) cisplatin-etoposide patients but not for any gemcitabine patients. Non-haematological toxicity was more pronounced with significant differences in nausea and vomiting (grade 3 and 4: 11% gemcitabine vs. 29% cisplatin-etoposide; despite the allowance for 5-HT3 antiemetics during the first cycle of cisplatin-etoposide), and alopecia (grade 3 and 4: 3% gemcitabine vs. 62% cisplatin-etoposide). Conclusions In this randomised study, single-agent gemcitabine was at least as active but better tolerated than the combination cisplatin-etoposid

Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene

The polymorphism SNP309 (rs2279744) in the promoter region of the MDM2 gene has been shown to alter protein expression and may play a role in the susceptibility to lung cancer. The MDM2 protein is a key inhibitor of p53 and several mechanisms of MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth and apoptosis

The association between active participation in a sports club, physical activity and social network on the development of lung cancer in smokers: a case-control study

<p>Abstract</p> <p>Background</p> <p>This study analyses the effect of active participation in a sports club, physical activity and social networks on the development of lung cancer in patients who smoke. Our hypothesis is that study participants who lack social networks and do not actively participate in a sports club are at a greater risk for lung cancer than those who do.</p> <p>Methods</p> <p>Data for the study were taken from the <b>Co</b>logne <b>Smo</b>king <b>S</b>tudy (<b>CoSmoS</b>), a retrospective case-control study examining potential psychosocial risk factors for the development of lung cancer. Our sample consisted of n = 158 participants who had suffered lung cancer (diagnosis in the patient document) and n = 144 control group participants. Both groups had a history of smoking.</p> <p>Data on social networks were collected by asking participants whether they participated in a sports club and about the number of friends and relatives in their social environment. In addition, sociodemographic data (gender, age, education, marital status, residence and religion), physical activity and data on pack years (the cumulative number of cigarettes smoked by an individual, calculated by multiplying the number of cigarettes smoked per day by the number of years the person has smoked divided by 20) were collected to control for potential confounders. Logistic regression was used for the statistical analysis.</p> <p>Results</p> <p>The results reveal that participants who are physically active are at a lower risk of lung cancer than those who are not (adjusted OR = 0.53*; CI = 0.29-0.97). Older age and lower education seem also to be risk factors for the development of lung cancer. The extent of smoking, furthermore, measured by pack years is statistically significant. Active participation in a sports club, number of friends and relatives had no statistically significant influence on the development of the cancer.</p> <p>Conclusions</p> <p>The results of the study suggest that there is a lower risk for physically active participants to develop lung cancer. In the study sample, physical activity seemed to have a greater protective effect than participation in a sports club or social network of friends and relatives. Further studies have to investigate in more detail physical activity and other club participations.</p

Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years

<p>Abstract</p> <p>Background</p> <p>Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis.</p> <p>Methods</p> <p>246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped.</p> <p>Results</p> <p>Genetic associations or gene-smoking interactions was found for <it>GPX1(Pro200Leu) </it>and <it>EPHX1(His113Tyr)</it>. Carriers of the Leu-allele of <it>GPX1(Pro200Leu) </it>showed a significant risk reduction of OR = 0.6 (95% CI: 0.4–0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1–0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of <it>EPHX1(His113Tyr) </it>for moderate smokers (OR = 0.2, 95% CI:0.1–0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07–0.60) for each protective allele.</p> <p>Conclusion</p> <p>Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of <it>GPX1(Pro200Leu) </it>and the C-Allele of <it>EPHX1(His113Tyr) </it>to play a protective role in early onset lung cancer susceptibility.</p