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© Oxford University Press 2007.
IN THIS ISSUE
Adverse Drug Interactions Among Cancer PatientsCancer patients typically receive numerous medications, including chemotherapeutic agents, drugs for supportive care, and treatments for conditions that coexist with the cancer. Riechelmann et al. (p. 592) report on the extent to which drug combinations with the potential for adverse reactions were prescribed to a sample of adult cancer patients receiving chemotherapy. Potential adverse interactions were identified using a computer software program that searched a database on drug interactions compiled from the published literature. At least one potentially adverse drug interaction was identified in 27% of the surveyed patients. The majority of the potential interactions were of moderate severity, and nearly half were supported by strong scientific evidence.
In an accompanying editorial, Norton and Baker (p. 579) discuss measures that would reduce the risk of adverse drug reactions, including designating a single primary care physician, improving coordination among the patients’ doctors and providers, and making effective use of information technology to oversee medication ordering, administration, and monitoring.
Assessment of Chemotherapy for High-risk Gastric Cancer Patients
The 5-year survival rate for patients with gastric cancer is poor, ranging between 15% and 35%. Although postoperative chemotherapy for gastric cancer has shown promise, its value not been demonstrated unequivocally. Cascinu et al. (p. 601) compared an intensive postsurgical chemotherapy regimen of four drugs with a traditional chemotherapy regimen based on 5-fluorouracil in 400 high-risk gastric cancer patients. The intensive regimen did not confer a survival benefit compared with the traditional one, and the extent of toxicity experienced by patients suggested that preoperative chemotherapy may be a more viable approach.
In an accompanying editorial, Ellenberg and Sun (p. 580) discuss potentially unforeseen factors that can render clinical trials of new treatments inconclusive. They underscore the importance of including rigorously designed control arms when evaluating new treatments as opposed to relying on historical controls.
Long-Term Daily Use of Adult-Strength Aspirin and Cancer Risk
Some studies have reported associations between aspirin use and reduced cancer risk, but the results have not been conclusive. To examine the association between long-term daily use of adult-strength aspirin and cancer, Jacobs et al. (p. 608) estimated the overall risk of cancer and the specific risks of 10 types of cancer among more than 145,000 participants in the Cancer Prevention Study II Nutrition Cohort. Participants reported aspirin use at enrollment in 1992–1993, and three more times between 1997 and 2001. From 1992 through 2003, 18,127 participants developed cancer. Daily use of adult-strength aspirin for 5 years or longer was associated with a reduced incidence of cancer overall among men (2,163 vs. 1,858 per 100,000 person-years) and women (1,169 vs. 1,083 per 100,000 person-years) compared with no use. Aspirin use was also associated with reduced risk of colorectal, prostate, and possibly breast cancer. The authors conclude that long-term daily use of adult-strength aspirin may be associated with reduced cancer incidence in populations among which these cancers are common.
In a related editorial, Martínez and Greenberg (p. 582) warn that for the average person, the side effects of long-term aspirin use—especially at doses greater than that defined as low (80 mg per day)—may outweigh the benefits for cancer prevention that have been observed to date. However, they note that aspirin may be useful in future cancer control strategies.
EGFR and Notch Signaling Pathways in Primary DCIS
The epidermal growth factor receptor (EGFR) and Notch signaling pathways have been implicated in the self-renewal of normal breast stem cells. To examine the involvement of these pathways in the growth of ductal carcinoma in situ (DCIS) of the breast, Farnie et al. (p. 616) examined how efficiently cells from DCIS and normal breast tissues grew as mammosphere cultures (i.e., nonadherent cells) in the presence of an EGFR inhibitor, gefitinib, or of two inhibitors of the Notch signaling pathway. In the mammosphere cultures, EGFR was necessary for DCIS growth and self-renewal, and Notch signaling was important for DCIS cell survival and/or self-renewal. The authors suggest that this culture method may facilitate the testing of novel agents to prevent DCIS recurrence and progression.
p95HER2 and HER2-targeted Breast Cancer Therapies
Many breast cancers that express the receptor tyrosine kinase HER2 are resistant to the HER2 antibody trastuzumab. Some breast tumors are resistant because they express p95HER2, a truncated form of the receptor that cannot bind to trastuzumab. To determine whether p95HER2 is sensitive to the tyrosine kinase inhibitor lapatinib, Scaltriti et al. (p. 628) measured the growth of xenograft breast cancer tumors in mice treated with either drug. They also developed an immunofluorescence assay to determine whether tumors of breast cancer patients who had become resistant to trastuzumab expressed p95HER2. The p95HER2-expressing xenograft tumors were resistant to trastuzumab but sensitive to lapatinib. Only a small percentage of patients whose tumors expressed the shortened p95HER2 responded to trastuzumab treatment, whereas the majority of patients whose tumors expressed full-length HER2 responded. The authors conclude that additional or alternative HER2-targeted therapies may improve the outcomes of breast cancer patients with p95HER2-expressing tumors.
Stathmin and Resistance of Malignant Gliomas to Nitrosoureas
Although malignant gliomas are generally resistant to all conventional therapies, patients with anaplastic oligodendrogliomas with loss of heterozygosity on the short arm of chromosome 1 (1p+/–) frequently respond to combination chemotherapy that includes a nitrosourea. Ngo et al. (p. 639) used malignant glioma cell lines to identify differentially expressed proteins encoded on 1p and examined whether their expression was associated with disease outcome. Decreased expression of stathmin, a microtubule-associated protein, was associated with loss of heterozygosity in 1p and with increased recurrence-free survival. Nitrosourea induced glioma cells to undergo mitotic arrest, and it had a greater effect in cells with decreased stathmin expression. The authors conclude that loss of heterozygosity for the stathmin gene may be associated with improved outcomes of patients with 1p+/– anaplastic oligodendroglioma tumors.
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J Natl Cancer Inst 2007 99: 579-580.
J Natl Cancer Inst 2007 99: 580-582.
J Natl Cancer Inst 2007 99: 582-583.
J Natl Cancer Inst 2007 99: 592-600.
J Natl Cancer Inst 2007 99: 601-607.
J Natl Cancer Inst 2007 99: 608-615.
J Natl Cancer Inst 2007 99: 616-627.
J Natl Cancer Inst 2007 99: 628-638.
J Natl Cancer Inst 2007 99: 639-652.
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