© 2003 by Oxford University Press
© 2003 Oxford University Press
IN THIS ISSUE |
Although surgery is the primary treatment for patients with stage I, II, or IIIA non–small-cell lung cancer (NSCLC), the long-term survival of these patients is poor. Scagliotti et al. (p. 1453) conducted a randomized trial to examine the effects of mitomycin C, vindesine, and cisplatin every 3 weeks for three cycles (MVP group) or no treatment (control group) on patient survival after complete resection of NSCLC. The authors found no difference in overall or progression-free survival between the two patient groups. Among patients in the MVP group, only 69% were able to receive all three cycles of planned chemotherapy, and grades 3 and 4 neutropenia occurred in 16% and 12% of patients, respectively. Radiotherapy was completed by 65% of patients in the MVP group and by 82% of patients in the control group. The authors conclude that the MVP regimen provides no clinically significant survival benefit for patients with NSCLC.
In an editorial, Johnson (p. 1422) discusses how the inclusion of patients with stage I NSCLC, the MVP chemotherapy regimen selected, and the incorporation of chest irradiation into the treatment of some of the patients may have impacted patient outcome in this study, thus potentially complicating the interpretation of the trial results. He suggests that future trial designs should include appropriate disease stages and treatment regimens that can be tolerated after surgical resection.
Interval Carcinomas in a Prostate Screening Trial
Interval cancer rates are important for determining the sensitivity and interval of a screening protocol. van der Cruijsen et al. (p. 1462) evaluated the time of detection and the stage distribution of interval prostate cancers diagnosed during a 4-year screening interval in a subset of men enrolled in the European Randomized Study of Screening for Prostate Cancer–Rotterdam. The authors identified 135 cancers among men in the control arm and, after the initial screen, 25 cancers among men in the screened arm during the 4-year interval. Excluding seven cancers diagnosed in men who refused a recommended biopsy during the initial screen, none of the 18 cancers was poorly differentiated or metastatic. The sensitivity of the screening protocol was 79.8% or 85.5%, depending on whether all 25 or 18 interval cancers were considered. The authors conclude that, with a low interval cancer rate and a high sensitivity screening procedure, the 4-year screening interval is reasonable.
Obesity, Tamoxifen Efficacy, and Breast Cancer Outcomes
Obese women with breast cancer have been found to have worse outcomes than lean women with the disease. The possible additional influence of obesity on treatment efficacy has not been addressed in most previous studies. To investigate the association of obesity with outcomes and tamoxifen efficacy, Dignam et al. (p. 1467) analyzed a cohort of women enrolled in a randomized trial evaluating tamoxifen as treatment for early-stage, hormone-responsive breast cancer. Obese women did not have a higher risk of breast cancer mortality or recurrence than lean women, but they did have higher risks of contralateral breast cancer, other primary cancers, and overall mortality. Tamoxifen reduced breast cancer recurrence and mortality in all women. The authors conclude that their findings support the use of tamoxifen for breast cancer patients of all body types.
Using COX-2 Inhibitors to Enhance Radiation Therapy
Results of preclinical studies suggest that the efficacy of molecular therapies is enhanced when they are combined with radiation. Choy and Milas (p. 1440) review the literature to identify the rationale and experimental foundation supporting the use of cyclooxygenase-2 (COX-2) inhibitors with standard radiation therapy regimens in current clinical trials. They describe clinical trial results demonstrating that selective inhibition of COX-2 can alter the development and the progression of cancer, results from studies of animal models showing that selective inhibition of COX-2 activity is associated with the enhanced radiation sensitivity of tumors without appreciably increasing the effects of radiation on normal tissue, and preclinical evidence suggesting that the principal mechanism of radiation potentiation through selective COX-2 inhibition is the direct increase in cellular radiation sensitivity and the direct inhibition of tumor neovascularization.
Selenium Supplementation and Nonmelanoma Skin Cancer
Duffield-Lillico et al. (p. 1477) present the final report of the Nutritional Prevention of Cancer Trial, a double-blind, randomized, placebo-controlled clinical trial that tested whether selenium supplementation could prevent nonmelanoma skin cancer among patients who previously had the disease. Although results of the entire blinded period continue to show that selenium supplementation was not associated with the risk of basal cell carcinoma, supplementation was statistically significantly associated with an increased risk of squamous cell carcinoma and of total nonmelanoma skin cancer. The authors conclude that, among individuals at high risk of nonmelanoma skin cancer, selenium supplementation is ineffective at preventing basal cell carcinoma and increased the risk of squamous cell carcinoma and total nonmelanoma skin cancer.
Germline BRCA1 Mutations and a Basal Epithelial Phenotype
A basal epithelial phenotype is associated with breast cancers that express neither the estrogen receptor (ER) nor erbB-2 (HER2/neu) (i.e., ER/erbB-2–negative tumors). The ER/erbB-2–negative phenotype is also found in breast cancers in patients with BRCA1 mutations (i.e., BRCA1-related tumors). Foulkes et al. (p. 1482) investigated whether BRCA1-related breast cancers were more likely than non–BRCA1-related and/or non–BRCA2-related breast cancers to express a basal epithelial phenotype, as reflected by the expression of cytokeratin 5 and/or 6. They found that the expression of the basal epithelial phenotype was statistically significantly associated with BRCA1-related breast cancers. They conclude that germline BRCA1 mutations appear to be associated with a distinctive breast cancer phenotype that can be detected by simple immunohistochemical assays.
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