Highlights In Journal Of The National Cancer Institute
The drug finasteride had a minimal effect on the sexual function of men who took it to prevent prostate cancer.
Some studies have found a link between finasteride and sexual dysfunction in men. But these studies were smaller, short-term, and did not consider variation among individuals when evaluating the impact of finasteride on sexual function.
Carol Moinpour, Ph.D., of the Fred Hutchison Cancer Research Center in Seattle and colleagues investigated sexual dysfunction in more than 17,000 men who participated in the Prostate Cancer Prevention Trial during a 7-year period.
Finasteride only slightly increased sexual dysfunction compared with a group not taking the drug, and the effect decreased over time.
"Our data show that the effects of finasteride treatment are clinically far less relevant than natural sources of variability in this heterogeneous population and suggest that finasteride would cause little or no sexual dysfunction for most men who might take it"the authors write.
Contact: Dean Forbes, communications department, Fred Hutchison Cancer Research Center
Surrogate Endpoints Inconsistently Used in Clinical Trials
In a commentary, Cornelis Punt, M.D., Ph.D., of the University Nijmegen Medical Center in The Netherlands and colleagues discuss the inconsistent use of surrogate endpoints in clinical trials and propose guidelines for future studies.
Overall survival is considered the gold standard endpoint for cancer treatment trials. But the time and money required to conduct a trial using overall survival as the endpoint has led researchers to consider other endpoints that can act as surrogates for overall survival.
Looking at 52 studies of phase III clinical trials of colon cancer treatment, the researchers found that eight other endpoints were used in addition to overall survival. Moreover, the definitions of these endpoints varied widely among studies.
A panel of clinical trial experts reached a consensus on definitions for the endpoints and determined if and when they should be used in future trials. Six of the endpoints were selected as relevant to treatment trials: disease-free survival, time to recurrence, time to treatment failure, relapse-free survival, cancer-specific survival, and overall survival.
"After considering all six endpoints, the panel selected disease-free survival as the most appropriate primary endpoint for future trials of adjuvant treatment for colon cancer or for any type of cancer. This endpoint was selected because it includes all clinically relevant events, has little opportunity for bias, is observed earlier than overall survival, and is likely to be statistically sensitive to real treatment benefits," the authors write.
Contact: Cornelis Punt
New Trial Design May Better Test Targeted Therapies
A new design for phase III trials will allow researchers to more efficiently evaluate the effectiveness of targeted therapies.
Many cancer drugs that target specific molecules only benefit a subset of patients who have high enough levels of the target molecule. Often, though, phase III clinical trials are designed without knowledge of this threshold, so the trial includes patients who will not respond to the treatment. That means the drug's effect on the group of responsive patients could be missed.
Wenyu Jiang, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues propose a different trial design that combines the usual test for response to treatment in all patients with the identification and validation of a cutoff point for a molecular target. They tested the design in a simulated trial and also used it to analyze data from an existing prostate cancer trial.
In the simulation trial, the new design allowed the researchers to see when the drug was effective in the overall population, as well as when it was effective in only a smaller subset with elevated levels of the target molecule.
"The procedure we have proposed allows drug development to be optimized by combining definitive testing for overall effect with biomarker validation," the authors write.
Sentinel lymph node biopsy is associated with breast cancer rates
The incidence of some early stage metastatic breast cancers is increasing, but this finding is likely explained by changes in clinical practice, according to a study published online in the Journal of the National Cancer Institute.
Deirdre Cronin-Fenton, Ph.D., of Aarhus University Hospital in Denmark, with colleagues at the National Cancer Institute in Bethesda, Md., found that the increase in some early stage breast cancers corresponded to greater use of biopsies of sentinel lymph nodes - the primary lymph node to which cancer cells are likely to spread from a tumor. Sentinel lymph node biopsies often detect small numbers of tumor cells that do not necessarily indicate that the cancer has spread.
"While the use of [sentinel lymph node biopsy] in community practice continues to increase, it is expected that cases with [lymph node] metastases also will continue to increase," the authors write.
Contact: Brenda Edwards, surveillance research program, National Cancer Institute
Citation: Cronin-Fenton DP, Ries LA, Clegg LX, Edwards BK. Rising Incidence Rates of Breast Carcinoma With Micrometastatic Lymph Node Involvement. J Natl Cancer Inst 2007; 99: 1044-1049
Nanoparticles carry chemotherapy drug deeper into solid tumors
A new drug delivery method using nano-sized molecules to carry the chemotherapy drug doxorubicin to tumors improves the effectiveness of the drug in mice and increases their survival time, according to a study published online in the Journal of the National Cancer Institute.
In the past, similar drug carriers have improved targeted delivery of the drugs and reduced toxicity, but they sometimes decreased the drugs' ability to kill the tumor cells. Using a new drug carrier, Ning Tang of the Chinese Academy of Sciences in Beijing and colleagues compared tumor growth and survival in mice that were given doxorubicin in the nanocarriers or on its own.
Doxorubicin delivered by nanocarriers was more effective in preventing tumor growth than free doxorubicin, and the mice receiving this treatment method lived longer and had fewer toxic side effects.
"Encapsulation of doxorubicin increased its accumulation and penetration in tumors in terms of both the percentage of cells that were reached by the drug and the intracellular levels that were attained," the authors write.
In an accompanying editorial, Matthew Dreher, Ph.D., of the National Institutes of Health in Bethesda, Md., and Ashutosh Chilkoti, Ph.D., of Duke University in Durham, N.C., discuss the future of drug delivery, which they think should focus on three important research areas - drug combinations, targeting, and integration.
"The study by Tang [and colleagues] is a simple but effective demonstration of the benefits of integration of a drug with an appropriate carrier to yield a striking gain in efficacy," the authors write. "May the days of pharmacological missiles that miss their target and friendly fire that kills patients soon be over!"
Contact:
* Article: Wei Liang,
* Editorial: Kendall Morgan, Duke University
Citations:
* Article: Tang N, Du G, Wang N, Liu C, Hang H, Liang W. Improving Penetration in Tumors With Nanoassemblies of Phospholipids and Doxorubicin. J Natl Cancer Inst 2007; 99: 1004-1015
* Editorial: Dreher MR, Chilkoti A. Toward a Systems Engineering Approach to Cancer Drug Delivery. J Natl Cancer Inst 2007; 99: 983-985
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Article adapted by Start Sanatate from original press release.
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The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Visit the Journal online at http://jnci.oxfordjournals.org/
Contact: Liz Savage
Journal of the National Cancer Institute
Evidenþiazã, în Jurnalul de la Institutul Naþional de Cancer - Highlights In Journal Of The National Cancer Institute - articole medicale engleza - startsanatate