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Sentinel Lymph Node Biopsy Versus Axillary TreatmentSentinel lymph node biopsy in women with operable breast cancer is used routinely in some countries for staging of the axilla despite limited data on morbidity and mortality outcomes. Mansel et al. (p. 599) conducted a multicenter randomized trial in patients with clinically node-negative invasive breast cancer to compare arm and shoulder morbidity and quality of life between those who received sentinel lymph node biopsy and those who received standard axillary treatment. In intention-to-treat analyses, the sentinel lymph node biopsy group experienced less lymphedema and sensory loss at 12 months than the standard axillary treatment group. The sentinel lymph node biopsy group had lower drain usage, shorter hospital stays and time to resumption of normal activities after surgery, and better overall patient-recorded quality of life and objective measures of arm function than the standard treatment group. The authors conclude that sentinel lymph node biopsy should be the treatment of choice for early-stage breast cancer patients with clinically negative nodes.
In an editorial, Pater and Parulekar (p. 568) discuss issues to consider in deciding whether widespread use of sentinel lymph node biopsy in the management of early-stage breast cancer is justified before its impact on relapse-free and overall survival is known.
Therapy Completion by Colon Cancer Patients
Several factors are associated with the initiation of adjuvant chemotherapy for stage III colon cancer. To investigate factors that predict the completion of colon cancer therapy, Dobie et al. (p. 610) analyzed Surveillance, Epidemiology, and End Results program data linked to Medicare claims data. Patients who were female, widowed, elderly, rehospitalized, or living in certain regions were less likely to complete therapy than other patients. Race and other clinical, environmental, and physician characteristics were not associated with completion of therapy. The authors conclude that factors associated with incomplete therapy may represent physical frailty, treatment complications, and the lack of physical and psychological support. Mitigation of these influences may increase therapy completion rates.
In an editorial, Grann and Muggia (p. 570) point out that the analysis confirmed the merits of completing therapy for optimal survival and note that the study brought into focus the increasingly important effect of age. They conclude that prospective studies are required to validate the predictors for therapy completion identified by this study.
Reporting of Clinical Trials in Hodgkin Lymphoma
Randomized clinical trials (RCTs) are the best way to compare the efficacy of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was developed in 1996 to improve and standardize reporting of RCTs. Kober et al. (p. 620) compared the frequency of reporting of 14 items in RCTs in Hodgkin lymphoma before and after the introduction of CONSORT. They identified a total 242 RCTs published during 1966 through 2002. Only six of the items were addressed in 75% or more of the studies over the entire period, and most items that are necessary to address methodologic quality were reported by fewer than 20% of the studies. Although the frequency of reporting of some items improved over time, the authors conclude that the reporting levels of CONSORT items in RCTs for Hodgkin lymphoma remain inadequate, and they offer several suggestions for improving compliance.
Adenovirus-Mediated Glioma Cell Death
To determine how conditionally replicating adenoviruses cause cancer cell–specific lysis, Ito et al. (p. 625) infected human malignant glioma cells with conditionally replicating adenoviruses that were regulated by the human telomerase reverse transcriptase promoter (hTERT-Ad). They examined the cellular morphology of and the activation of signaling pathways involved in nonapoptotic cell death in glioma cells expressing telomerase that were infected with hTERT-Ad. The authors also compared tumor growth and survival of mice carrying xenograft telomerase-expressing gliomas that were treated with hTERT-Ad with those of mice treated with a control adenovirus. Glioma cells that were infected with hTERT-Ad underwent nonapoptotic cell death, and mice carrying gliomas that were treated with hTERT-Ad lived longer and had tumors that grew more slowly than mice treated with the control adenovirus. The authors conclude that hTERT-Ad may kill telomerase-positive cancer cells by inducing autophagic cell death.
Validation of a Lung Cancer Prediction Model
The Bach model was developed to predict the absolute 10-year risk of developing lung cancer among smokers by use of data from the Carotene and Retinol Efficacy Trial of lung cancer prevention. Cronin et al. (p. 637) assessed the validity of this model by use of 6239 smokers from the placebo arm of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The Bach model slightly underestimated the observed lung cancer risk over 10 years. Moreover, the competing risk portion of the model substantially underestimated risks of non–lung cancer mortality over 10 years. The authors conclude that periodic radiographic screening in the ATBC Study may explain why slightly more cancers were observed than were expected from the Bach model.
PK/PD Technologies in Clinical Trials
Clinical trials of new cancer drugs should ideally include measurements of parameters that can be linked to measures of clinical effect, such as molecular target expression, pharmacokinetic (PK) behavior, and pharmacodynamic (PD) endpoints. Appropriate PK/PD biomarkers facilitate proof-of-concept demonstrations for target modulation; enhance the selection of an optimal drug dose and schedule; aid decision-making; and may explain or predict clinical outcomes.In addition, measurement of PK/PD biomarkers can help predict drug safety and efficacy, reduce high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development. However, phase I trials of new cancer drugs often lack detailed information about PK and/or PD endpoints. Writing for the Pharmacodynamic/Pharmacokinetic Technologies Advisory Committee of Cancer Research UK, Workman et al. (p. 580) review minimally invasive PD/PK technologies, emphasizing magnetic resonance spectroscopy and positron emission tomography because they provide detailed functional and metabolic information, and discuss their strengths and weaknesses.
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