NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
September 12, 2006 • Volume 3 / Number 35 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Paclitaxel Fails as Ongoing Treatment for Metastatic Breast Cancer

Taxane drugs, such as paclitaxel, have shown effectiveness in helping to stabilize metastatic breast cancer and prolong the time to disease progression. However, whether chemotherapy should be continued once disease stabilization has been achieved is controversial. A new study from Italy, the Maintenance Paclitaxel 1 (MANTA1) study, has now shown that continuing paclitaxel treatment as maintenance therapy in patients whose cancer has been stabilized does not improve progression-free survival.

In the study, 238 patients with metastatic breast cancer and no evidence of disease progression after chemotherapy with paclitaxel and doxorubicin or epirubicin were randomly assigned to receive eight additional doses of paclitaxel, given once every 3 weeks, or no additional treatment. The study was stopped in 2002 when it became clear that there was no difference in progression-free survival or overall survival between the two patient groups. Some patients treated with paclitaxel experienced severe side effects from the drug, including a loss of white blood cells and nerve damage.

Lead author Dr. Alessandra Gennari of the National Cancer Research Institute in Genoa, Italy, and colleagues concluded in the August 20 Journal of Clinical Oncology that the policy of prolonging treatment after aggressive modern combination chemotherapy cannot be recommended for women with metastatic breast cancer.

Since the beginning of this study in 1998, administration of paclitaxel maintenance therapy has increased to once a week. Therefore, a possible benefit from more aggressive maintenance therapy cannot be ruled out.

New Treatment Pays Dividends in Pediatric Medulloblastoma

Significantly altering how both radiation and chemotherapy are used to treat children with medulloblastoma can significantly improve survival for patients with high-risk disease, according to clinical trial results released early online September 7 in Lancet Oncology.

Led by researchers from St. Jude Children's Research Hospital, the 134-patient study entailed giving patients with high-risk disease higher doses of radiation therapy and all patients a more "dose-intensive" chemotherapy regimen - that is, higher than usual doses for 4 months, instead of lower doses over 12 months, which is the current standard of care.

The 5-year event-free and overall survival rate for high-risk patients (metastatic disease or a tumor larger than 1.5 cm2 after surgery) was 70 percent compared with historical rates of 30 to 40 percent. High-risk patients with metastatic disease (who made up 85 percent of that group) had an overall survival rate of 66 percent.

"Meticulous staging and careful attention to detail during radiotherapy planning and treatment are essential to obtaining similar outcomes," said the study's lead author, Dr. Amar Gajjar, who directs the Division of Neuro-Oncology at St. Jude.

Among average-risk patients, 5-year event-free survival was 83 percent, on par with outcomes following standard chemotherapy regimens. The use of dose-intensive chemotherapy in average-risk patients, cautioned Dr. Howard Fine, chief of the NCI Neuro-Oncology Branch, may increase their chances of greater short-term and/or long-term toxicity "with no apparent benefit compared to historical controls." But a shorter overall length of treatment in the new dose-intense regimen also could reduce long-term morbidity, he continued, noting that future comparative trials will have to study these issues closely.

Finally, the results of a regimen tested in only a few select pediatric brain tumor centers of excellence may not be comparable to the historical data obtained from the often poorer outcomes seen when such treatment regimens are expanded to larger multi-institutional trials, Dr. Fine added.

Analyses of tumor samples, the study authors reported, confirmed earlier suggestions that patients whose tumor samples had activating mutations in the CTNNB1 gene are more likely to have superior outcomes.

70-Gene Signature for Breast Cancer Risk Validated

Researchers have independently validated a 70-gene signature created in 2002 to assess the risk of recurrence of breast cancer among certain women with node-negative disease. The signature, developed at the Netherlands Cancer Institute, has been used experimentally to identify patients who do not need adjuvant chemotherapy because the risk of recurrence is so low that withholding chemotherapy would not compromise long-term health.

The study to validate the 70-gene signature, or classifier, included 307 women with node-negative cancers and certain types of tumors. The classifier was more predictive of the risk of recurrence, the risk of distant metastatic recurrence, and death from any cause than were several standard clinical prognostic methods, the researchers reported in the September 6 Journal of the National Cancer Institute (JNCI).

"We believe the results justify proceeding to a prospective study," wrote Dr. Marc Buyse of the International Drug Development Institute in Brussels, and his colleagues in the TRANSBIG Consortium.

The validation study in JNCI, noted Dr. Richard Simon of NCI's Division of Cancer Treatment and Diagnosis in an accompanying editorial, did not evaluate the clinical utility of the classifier. According to Dr. Simon, this can only be accomplished by randomly assigning a defined group of patients to have their treatment determined on the basis of either 1) the gene classifier or 2) standard practice guidelines. If the patients in the first group have better outcomes than those in the second, then clinical utility is established.

ERCC1 Expression in Lung Cancer May Predict Survival Benefit from Cisplatin

A new substudy from the International Adjuvant Lung Cancer Trial (IALT) - the IALT Bio study - has identified lack of expression of the DNA-repair protein ERCC1 as a possible predictor of increased survival after cisplatin-based chemotherapy. The results, published in the September 7 New England Journal of Medicine, showed that patients whose tumors lacked ERCC1 expression derived a significant survival benefit from adjuvant cisplatin-based chemotherapy, but patients with ERCC1-positive tumors did not.

The IALT Bio investigators used immunostaining to evaluate ERCC1 expression in tumor and control tissue taken from 761 patients who participated in the IALT trial; 389 had received adjuvant cisplatin-based chemotherapy, and 372 were followed without further treatment after surgery. The investigators then compared overall survival within the chemotherapy and control groups based on ERCC1 status.

Expression of ERCC1 correlated with age, tumor histology, and whether the tumor had spread into the pleura. For patients with ERCC1-negative tumors, the addition of chemotherapy significantly improved 5-year overall survival, which was 47 percent in the chemotherapy group and 39 percent in the control group. The addition of chemotherapy did not significantly improve survival for patients with ERCC1-positive tumors.

"Our results suggest that determination of ERCC1 expression in non-small-cell lung cancer cells before chemotherapy can make a contribution as an independent predictor of the effect of adjuvant chemotherapy," stated the authors. The next question for researchers, explained Dr. Eddie Reed of the Centers for Disease Control and Prevention in an accompanying editorial, "is whether this information can be used prospectively."

Intervention Increases Mammography Rates Among Triracial Women

Lay health advisor (LHA) intervention improved mammography utilization and knowledge among rural, low-income white, African American, and Native American women in Robeson County, N.C., according to study results in the September 6 JNCI. Minority women and women of low socioeconomic status have lower rates of breast cancer screening and higher rates of breast cancer mortality.

The study, conducted from February 1998 through January 2002, included 851 women who were randomly assigned to the LHA intervention group or comparison group. Prior to group assignment, researchers conducted baseline interviews to gather information on breast cancer screening, cancer history, and social support, as well as knowledge of, beliefs on, and barriers to mammograms. The 9- to 12-month LHA intervention consisted of three in-person visits with a trained LHA who provided information about cancer risk and overcoming barriers to mammograms, and follow-up phone calls and mailings to encourage women to get a mammogram. The comparison group received a letter on getting a mammogram and an NCI brochure on cancer and mammography 3 and 6 months after random assignment. Both groups completed a follow-up survey at the study's culmination.

Researchers found that 42.5 percent of the women in the LHA intervention group and 27.3 percent in the comparison group received a mammogram in the 12 months before the follow-up assessment. In addition, women in the LHA intervention group showed an increase in knowledge about breast cancer screening and a reduced risk of reporting barriers to getting a mammogram, such as lack of encouragement, time, and cost of a mammogram.

The study's authors concluded that "Future research should examine cost-effective ways to disseminate such interventions. These strategies are needed to reduce the disparate burden of disease among underserved populations."