National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
June 16, 2009 • Volume 6 / Number 12

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Cancer Research Highlights

Treatment Regimen Extends Survival for Women with Cervical Cancer

Making the chemotherapy drug gemcitabine part of the initial treatment of locally advanced cervical cancer and also part of therapy following primary treatment significantly improved survival for women with locally advanced cervical cancer, according to the results of an international, phase III clinical trial.

Presented recently at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting, the results have important implications for the treatment of women with cervical cancer in developing countries, where 70 to 80 percent of women are diagnosed at a locally advanced stage due to a lack of widespread screening programs, said lead investigator Dr. Alfonso Dueñas-González of the National Cancer Institute of Mexico.

More than 500 women with stage IIB to stage IVA cervical cancer—from countries as disparate as Pakistan and Panama—participated in the trial. They were randomly assigned to the experimental treatment arm, which included cisplatin and gemcitabine with concurrent external-beam radiation therapy, followed by brachytherapy and adjuvant chemotherapy with gemcitabine and cisplatin. Women in the standard treatment group received cisplatin and concurrent external-beam radiation therapy followed only by brachytherapy.

Approximately 75 percent of women who received the experimental treatment did not experience progression of their disease 3 years after treatment, compared with 65 percent of women who received standard treatment. Overall survival was improved by more than 40 percent, the researchers reported. The research team had expected more toxicity with the addition of gemcitabine, and that is what they saw.

"Overall, the frequency of grade III and IV toxicities was higher in the experimental arm, mainly hematological toxicity," Dr. Dueñas-González said. Grade IV toxicities were low overall, he added, and generally toxicities in the experimental arm were "tolerable and manageable."

The trial "in all likelihood defines a new standard of care" for patients with locally advanced cervical cancer, said Dr. Eric Winer, chief of the Division of Women's Cancers at Dana-Farber Cancer Institute.

Standard Treatment for Anal Cancer Confirmed

The largest clinical study of patients with anal cancer has found that the current standard treatment should not be changed. In addition, patients in the study did not benefit from maintenance chemotherapy that was designed to prevent a recurrence, according to the ACT II study, a phase III, randomized trial involving 940 patients.

Most of the 5,000 patients diagnosed with anal cancer in the United States each year have the squamous cell type, which often responds to radiation therapy and chemotherapy. For a decade, the treatment for anal cancer has been radiation plus 5-fluorouracil (5-FU) and mitomycin-C chemotherapy. In this trial, British researchers asked whether replacing mitomycin-C with cisplatin could improve results for patients, but the answer was no. Furthermore, patients did not benefit from maintenance chemotherapy with cisplatin and 5-FU.

Overall, however, the patients had very good results relative to the international trials published to date, noted Dr. Roger James of the Maidstone Hospital in Kent, who presented the findings at the recent ASCO annual meeting. At 6 months, 95 percent of patients in both groups had all signs of cancer disappear, and at 3 years, nearly 85 percent of the patients in the trial were alive.

Cisplatin was evaluated because it is commonly used to treat other squamous cell cancers, the researchers said, noting that it is not as convenient to deliver and has different toxicities than mitomycin-C chemotherapy. Future trials will likely ask whether certain patients might benefit from other forms of maintenance therapy.

Donated Stem Cell Transplants Better than Self-transplants for Most Patients with AML

Evidence from a meta-analysis of prospective clinical trials supports the use of donated (or allograft) stem cell transplants (SCT) to treat individuals with acute myeloid leukemia (AML). The findings appeared June 10 in the Journal of the American Medical Association.

AML patients are usually classified as good-, intermediate-, or poor-risk, depending on genetic factors linked to the disease. Those in the good-risk group have the best chance of disease recovery and the lowest risk of relapse. The National Comprehensive Cancer Network states that those in the good-risk group should receive SCT from their own body after their initial chemotherapy, or a second round of chemotherapy if SCT is not possible; those in the poor-risk group should have an allograft SCT after chemotherapy; and those who have intermediate-risk disease can be treated either way, because it is not clear if one is better than the other.

Now, an international team of researchers led by Dr. John Koreth at the Dana-Farber/Harvard Cancer Center has reviewed the literature comparing allograft and non-allograft SCT, to determine what the evidence supports for patients in each risk group based on the rates of relapse-free survival and overall survival. The researchers reviewed 24 prospective clinical trials in the United States, Europe, and Japan that included 6,007 adult patients.

Patients who were in the good-risk groups showed no significant difference in relapse-free survival or overall survival if they received a SCT from their own body or from a donor. Those in the intermediate-risk and poor-risk groups, however, showed a clear benefit when receiving allograft SCT compared with SCT from their own bodies.

Overall, the researchers stated, the benefits of allograft SCT were markedly clearer for those in the intermediate- and poor-risk groups. But they noted that "there remains a need to further individualize the allogeneic SCT decision, based on factors like patient age, comorbidity, and the presence of additional molecular lesions."

Restoring MicroRNA Expression Stops the Spread of Liver Cancer in Mice

Researchers from the Johns Hopkins University School of Medicine have shown that restoring the expression of a single microRNA (miRNA) that had been lost in liver cancer cells could prevent tumor growth in mice. miRNAs are short strands of RNA that regulate the activity of genes, including some that are involved in cancer. The study results appeared June 12 in Cell.

The researchers chose the microRNA miR-26a, which is abundant in normal adult liver tissue but lacking in both human liver cancer (hepatocellular carcinoma or HCC) and in the mouse model of HCC used in their experiments.

After initiating liver tumor formation in their mouse model, the researchers restored miR-26a to the tumor cells by injecting a virus engineered to specifically target liver tissue. The virus contained the miR-26a gene and a gene for a fluorescent protein to allow the researchers to visualize successful transfer.

Eight out of 10 mice that received the virus containing the miR-26 gene developed only small tumors or did not develop measurable tumors. The two mice that did develop aggressive tumors had significantly less of the miR-26a gene successfully delivered to their liver tissue. Six out of eight control mice that did not receive the miR-26a gene developed aggressive disease.

miR-26a is not thought to target a specific oncogene responsible for initiating liver tumors. Instead, it worked by generally inhibiting cancer cell proliferation and inducing apoptosis (cell death). No measurable effects were seen in normal liver cells, likely due to their naturally high levels of the miRNA.

The study "provides proof-of-principle that the systemic administration of miRNAs may be a clinically viable anticancer therapeutic strategy," concluded the authors.

Among the Elderly, Adverse Events from Colonoscopy Are Rare

Older individuals who undergo outpatient colonoscopy have a low risk of adverse events, but the risk increases with advancing age and in individuals with certain health conditions, such as diabetes, stroke, and congestive heart failure. The findings are from the first study to assess complications from outpatient colonoscopy in older individuals. NCI researchers analyzed the Medicare records of 53,220 people aged 66 to 95 who underwent colonoscopy between 2001 and 2005.

"Colorectal cancer screening is very important for the prevention of this disease, and we need to know whether colonoscopy is a safe method of colorectal cancer screening as a person gets older and whether there are specific health conditions that can increase one's risk," said lead investigator Dr. Joan Warren of NCI's Division of Cancer Control and Population Sciences. "Until now there have been no data on these questions out there."

As the researchers reported today in the Annals of Internal Medicine, the risk of a serious gastrointestinal event within 30 days following colonoscopy was 6.9 per 1,000 procedures. However, the risk of a serious gastrointestinal event for persons aged 85 and older was more than twice that for persons aged 66 to 69.

The results are consistent with recommendations made last October by the U.S. Preventive Services Task Force, noted Dr. Warren. The Task Force advised against colorectal cancer screening in adults older than age 85 because the potential benefits were small compared to the risks. The group also recommended against routine screening for individuals aged 76 to 85.

The findings will likely contribute to an ongoing debate about the use of screening colonoscopy among individuals who have a limited life expectancy because of advanced age or existing health conditions. In their report, the researchers urged clinicians to incorporate the results into their discussions with patients about the risks of colonoscopy.