© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 3, 175,
February 2, 2000
© 2000 Oxford University Press
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Hortobagyi et al. (p. 225) have conducted a prospective randomized trial involving women with high-risk (of relapse) breast cancer to compare the outcomes of patients treated with standard-dose chemotherapy and patients treated with the same therapy followed by high-dose chemotherapy. Seventy-eight women received eight cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. They were then randomly assigned to receive no further treatment or to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support (bone marrow transplantation). The authors report no relapse-free or overall survival advantage associated with the use of high-dose chemotherapy and note that morbidity was increased with this therapeutic approach. They conclude that, at present, high-dose chemotherapy for high-risk breast cancer is not indicated outside a clinical trial.
"Although this was a small trial designed to detect a 30% difference in 3-year relapse-free survival, it accomplished its goal and ruled out a large reduction in risk associated with high-dose chemotherapy."
—Hortobagyi et al.
New Treatment Response Guidelines
In a special article (p. 205), Therasse et al. present a new set of guidelines for evaluating the response of solid tumors to anticancer treatments. These RECIST (Response Evaluation Criteria in Solid Tumors) guidelines are the result of a large, international collaboration and are based on criteria established by the World Health Organization (WHO) in 1979. They are intended to simplify and further standardize the evaluation and reporting of treatment responses, primarily in the context of randomized clinical trials. These guidelines incorporate the use of unidimensional measurement of tumor size as opposed to bidimensional measurement.
In an accompanying editorial, Gehan and Tefft (p. 179) discuss the potential role of the RECIST guidelines in the evaluation of solid tumors. The editorial writers also compare and contrast the new guidelines with the original WHO guidelines, which are based on bidimensional measurement of tumors.
Indanocine: Antimitotic Agent and Inducer of Apoptosis
Antimitotic agents are generally thought to target the protein tubulin and interfere with cellular processes involving microtubule assembly/disassembly. Certain antimitotic agents, however, have antitumor activities that apparently result from interaction with nontubulin components of the cell involved in proliferation and/or apoptotic cell death. Leoni et al. (p. 217) describe the activities of the antimitotic drug indanocine. They report that indanocine interacts with tubulin at the colchicine binding site, inhibiting tubulin polymerization in vitro and disrupting mitosis in cultured cells. In experiments with proliferating cells, three of seven multidrug-resistant cell lines tested were more sensitive to growth inhibition by indanocine than their drug-sensitive counterparts. Furthermore, indanocine induced apoptotic cell death in stationary-phase multidrug-resistant cancer cells at concentrations that did not impair normal nonproliferating cells.
In an accompanying editorial, Giannakakou et al. (p. 182) note that many agents that target tubulin have been effective against many types of cancers. However, they caution that additional experiments are needed to determine whether indanocine will be an effective chemotherapeutic agent for treating cancer and multidrug-resistant tumors.
Reminder Calls and Screening Mammograms
Previous studies have shown that motivational telephone calls addressing women’s concerns about the risks and benefits of mammography increase their adherence to regular screening appointments compared with a simple reminder letter. Taplin et al. (p. 233) conducted a randomized trial to test the effectiveness of motivational calls compared with simple reminder calls and reminder letters. Women who received motivational calls were no more likely to schedule a mammogram than women who received reminder calls; women in both these groups were more likely to get mammograms than women who were mailed postcards. The authors say that a simple intervention such as a reminder phone call would have distinct economic advantages where intervention resources are limited.
Coumarin Antibiotics and Heat Shock Protein 90
Heat shock protein 90 (Hsp90) stabilizes several oncogenic protein kinases (e.g., p185erbB2, p60v-src, and Raf-1) and is required for the stability and dominant–negative function of mutated p53 protein. Two unrelated antibiotics, geldanamycin and radicicol, bind to Hsp90, and this interaction leads to cellular depletion of Hsp90 binding partners. Marcu et al. (p. 242) tested whether three coumarin antibiotics—novobiocin, chlorobiocin, and coumermycin A1—could also interact with Hsp90 and interfere with its stabilizing function. They found that novobiocin binds a carboxy-terminal domain of Hsp90, whereas geldanamycin and radicicol bind an amino-terminal domain. Furthermore, the three coumarin antibiotics markedly reduced cellular levels of p185erbB2, p60v-src, Raf-1, and mutated p53. The authors say that coumarin antibiotics, particularly novobiocin, may represent a first-generation alternative to other Hsp90-targeting drugs that are not as well tolerated.
Talc Use and Ovarian Cancer
The association between perineal use of talcum powder and ovarian cancer remains controversial because of potential biases in previous studies and limited supporting biologic evidence. Gertig et al. (p. 249) conducted a prospective analysis of perineal talc use and ovarian cancer in a cohort of 78,630 women among whom 307 epithelial ovarian cancers were subsequently diagnosed. They found no overall association between ever use of talc and epithelial ovarian cancer and no increase in risk of ovarian cancer with increasing frequency of talc use. There was a modest elevation of risk for ever use of talc and invasive serous ovarian cancer, a histologic subtype of the disease. Gertig et al. note that limitations of the study include a relatively short follow-up period of 15 years and a lack of information on the age at which women began using talc and on the duration of use.
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