Experimental Drug for Osteosarcoma Improves Overall Survival

Patients with osteosarcoma who received the experimental drug mifamurtide (L-MTP-PE) along with chemotherapy fared better than patients who received chemotherapy alone, researchers are reporting. Osteosarcoma is a rare but often fatal cancer of the bone. The disease typically affects children and young adults, and no new therapies have been introduced in two decades.

The study – conducted by the Children’s Oncology Group – was the largest final-stage randomized trial in this disease and included 662 patients with newly diagnosed nonmetastatic osteosarcoma.

After 6 years of follow-up, overall survival was 78 percent in the group receiving mifamurtide plus chemotherapy compared with 70 percent in the group receiving chemotherapy alone. “This is an almost one-third reduction in the risk of death,” write Dr. Paul A. Meyers of the Memorial Sloan-Kettering Cancer Center and his colleagues in the February 1 Journal of Clinical Oncology.

A second goal of the NCI-sponsored study was to evaluate the addition of ifosfamide to the three chemotherapy drugs used in the study (cisplatin, doxorubicin, and methotrexate). Adding this agent did not enhance event-free survival or overall survival for patients in the trial.

As an experimental agent, mifamurtide is available only through clinical trials. In 2006, its manufacturer, IDM Pharma, sought approval for its use in treating osteosarcoma from the Food and Drug Administration, but the agency requested more information. The company plans to submit new data showing an overall survival benefit in the disease this year.

Source: NCI Cancer Bulletin. February 19, 2008

Preventing Chemotherapy-Induced Neuropathy

Name of the Trial
Phase III Randomized Study of Alpha-Lipoic Acid in Preventing Platinum-Induced Peripheral Neuropathy in Cancer Patients Receiving a Cisplatin- or Oxaliplatin-Containing Chemotherapy Regimen (MDA-CCC-0327). See the protocol summary at http://cancer.gov/clinicaltrials/MDA-CCC-0327. Principal Investigator
Dr. Ying Guo, University of Texas M.D. Anderson Cancer Center

Why This Trial Is Important
Peripheral neuropathy is a condition characterized by sensations of pain, tingling, burning, numbness, or weakness that usually begin in the hands or the feet. It can be caused by certain illnesses, for example, diabetes. It can also be a side effect of treatment with platinum-based chemotherapy drugs.

The peripheral neuropathy associated with platinum-based chemotherapy can be either acute or chronic. Acute peripheral neuropathy may begin during or shortly after administration of a platinum-containing drug and usually goes away on its own after several days. Chronic peripheral neuropathy may arise weeks or months after chemotherapy treatment and may be difficult to treat; in some patients, it may be irreversible.

In this trial, researchers are testing the ability of alpha-lipoic acid to prevent peripheral neuropathy caused by the platinum-containing drugs cisplatin and oxaliplatin. Alpha-lipoic acid is an antioxidant produced naturally by the body; it can also be found in some foods and as a nutritional supplement. In patients with diabetes, it has been shown to relieve symptoms of neuropathy.

“Peripheral neuropathy is a potentially disabling condition that affects many cancer patients treated with platinum-based chemotherapy,” said Dr. Guo. “We hope that alpha-lipoic acid will help prevent this condition in patients undergoing chemotherapy with cisplatin or oxaliplatin.”

Patients in this trial will be randomly assigned to receive oral alpha-lipoic acid or a placebo three times a day for at least 24 weeks.

Source: NCI Cancer Bulletin. February 19, 2008

Large Majority of Breast Cancer Information on Internet Is Accurate

Approximately 95% of information about breast cancer that is found on the Internet is accurate. These results were recently published in the journal Cancer.  The Internet provides a wealth of information on all aspects of health-related issues. A majority of patients now report that they seek health information on the Internet. Online information, however, is not strictly regulated, which has made some healthcare providers skeptical of the Internet as a source for healthcare information. Reviewers continue to assess the accuracy of online healthcare information.

Researchers from Texas recently conducted a clinical study to evaluate the accuracy of information about breast cancer on the Internet. This study included 343 unique Web pages found from breast cancer-related queries entered on five search engines. Researchers also attempted to establish criteria to help identify inaccurate information on these pages.

• Inaccurate statements were made on 18 Web pages, which amounted to 5.2% of Web pages reviewed.
• Inaccurate statements were significantly more likely to be found on Web pages that also presented information on complementary and alternative medicine (CAM).
• There were no other identified criteria associated with inaccurate statements.

The researchers concluded: “Most breast cancer information that consumers are likely to encounter online is accurate.”  The authors also noted: “Webpages that contain information about CAM are relatively likely to contain inaccurate statements.” 

Patients with breast cancer are encouraged to always seek expert advice directly from their healthcare providers.

Source: Cancer Consultants

Clinical Outcomes in Colon Cancer Linked to microRNA Gene

Colon tumors that produced high expression levels of a microRNA gene called miR-21 were associated with poor survival and therapeutic outcome in two patient populations, one in the U.S. and the other in China, according to a study in the January 30 Journal of the American Medical Association.

Like other microRNA genes, miR-21 produces short strands of RNA that control multiple genes, including some involved in cancer. The findings support a growing view that this gene, which shows increased activity in more than a dozen major cancers, may be a useful biological marker and therapeutic target.

“We are interested in this gene in part because our results may have implications for other cancers,” said Dr. Curtis Harris of NCI’s Center for Cancer Research (CCR), who led the study. “And a therapy directed against miR-21 may be effective against a variety of cancers.” He cautioned that the results are preliminary and potential therapies may be years away.

The researchers first profiled microRNA gene activity in colon tumors and matched normal tissues from 84 patients from Maryland, and they validated the results in 113 patients from Hong Kong. The most striking finding was the association between high miR-21 activity in tumors and poor survival and therapeutic outcome in patients receiving adjuvant chemotherapy based on 5-fluorouracil. The associations were consistent even though slightly different techniques were used to assess microRNA activity in each group.

The results also indicate that microRNA gene activity is systematically altered in colon tumors compared to normal tissues. “There are systematic changes in microRNA expression during the cancer process,” said first author Dr. Aaron Schetter of NCI’s CCR.

Source: NCI Bulletin. February 5, 2008

Oral Contraceptives Reduce Long-Term Risk of Ovarian Cancer

Since they were first licensed nearly 50 years ago, birth control pills containing estrogen have prevented some 200,000 cases of ovarian cancer world-wide, estimate the authors of a study published January 26 in The Lancet. Further, in the absence of having taken oral contraceptives, half of these women would have died of the disease.

The researchers showed that oral contraceptives (OCs) continue to confer protection for years – even decades – after women stop using them. Thus, they surmise, “the number of ovarian cancers prevented [will] rise over the next few decades” to at least 30,000 each year.

These figures emerge from a comprehensive meta-analysis based on prospective and case-control data from 45 epidemiological studies in 21 countries, mostly in Europe and the United States. “These findings set a new standard in prevention for a deadly cancer,” wrote the editors of The Lancet, “and have important public health implications.”

The results showed that women who had ever taken OCs were 27 percent less likely to develop ovarian cancer. The studies included 23,257 women with ovarian cancer, 31 percent of whom had taken OCs; of the 87,303 controls, 37 percent took OCs.

Two trends emerged that were really striking, according to Dr. Beth Karlan, editor-in-chief of Gynecologic Oncology and director of the Gilda Radner Cancer Detection Program at Cedars-Sinai Outpatient Cancer Center in Los Angeles. First, the longer OCs were used, the greater the ovarian cancer risk reduction, decreasing about 20 percent for each 5 years of use.

The second clear trend was the duration of the protective effects, which lasted long after women had stopped using OCs. For each 5 years of use, risk of developing ovarian cancer was reduced 29 percent in the first 10 years after stopping. The risk reduction was still significant though smaller (19 percent) for years 10–20, and smaller still (15 percent) 20–29 years after discontinuation.

Another feature of these results is their uniformity. OCs seem to protect against nearly all types of epithelial and nonepithelial tumors, with the possible exception of mucinous ovarian cancer (which accounted for only 12 percent of cases studied in the meta-analysis). The Lancet editorial points out that the results show “the benefits of oral contraceptives are independent of the preparation [estrogen dose], and vary little by ethnic origin, parity, family history of breast cancer, body-mass index, and use of hormone replacement therapy.”

Representatives from nearly all of these studies – including Drs. Patricia Hartge, James Lacey, Louise Brinton, and Robert Hoover from the Epidemiology and Biostatistics Program in NCI’s Division of Cancer Epidemiology and Genetics (DCEG) – worked together to ensure the integrity of the analysis, forming the Collaborative Group on Epidemiological Studies of Ovarian Cancer, under the leadership of Dr. Valerie Beral and colleagues at Oxford University’s Cancer Research UK Epidemiology Unit.

The absence of proven screening methods for ovarian cancer make these findings all the more welcome. But the issue is not straightforward, because calculating “the net effect on women’s health is fraught with uncertainties,” wrote Drs. Eduardo L. Franco and Eliane Duarte-Franco of McGill University in Montreal in a comment accompanying the article. They went on to list possible consequences for OCs as increased risk of thromboembolism, heart disease, migraine, liver disease, and several other relatively uncommon conditions.

The analyses were not focused on comparing the benefits and risks of OCs, explains DCEG’s Dr. Brinton, but only examined their effect on ovarian cancer risk. In the absence of detailed risk-benefit data, including currently unknown risks, such as cancers in women who have taken OCs and later take long-term hormone replacement therapy, she says, “This meta-analysis does not recommend widespread prescription of OCs as a preventative measure against ovarian cancer.”

Dr. Beral commented that while OCs may pose a slight increased risk of breast and cervical cancer, the effect is small and disappears once the drugs are no longer being used, as contrasted with the ongoing protective effect against ovarian cancer.

Dr. Karlan added, “Ovarian cancer remains a disease with a high mortality due [mainly] to our inability to reliably diagnose it at an early stage. Women are concerned about this risk.” She noted that it is important for women to be aware that OCs reduce that risk when discussing their contraceptive choices with their health care providers.

Source: NCI Cancer Bulletin. February 5, 2008