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Discoveries in personalized and complementary medicine from ASCO

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  2. Discoveries in personalized and complementary medicine from ASCO

More than 4000 abstracts were presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) held June 4 through 8,2010, in Chicago, Illinois. Here are highlights from 3 studies presented there.

Heart Problems Linked to Genes and Dose Levels

Childhood cancer survivors who carry specific variants of the CBR gene and also received low doses of anthracycline chemotherapy were much more likely to develop heart disease than patients who received low doses but did not have these genetic variants, according to a study by the Children's Oncology Group. To the authors' knowledge, the study is the first of its kind examining the connection between these genes, anthracycline dose levels,and cardiomyopathy.

Although nearly 80% of childhood cancer patients survive, manymust dealwith health problems such as heart disease later in life. “Once cardiomyopathy develops, it is associated with a 2-year survival rate of less than 50%,” notes senior author Smita Bhatia, MD, MPH, professor and chair of the department of population sciences at the City of Hope National Medical Center in Duarte, California. The medical community has known for 30 years that anthracyclines can trigger heart disease, but they have not been able to establish safe dosage levels or explain the variability of side effects noted among patients who receive the drugs. Carbonyl reductases (CBRs) are enzymes that help metabolize anthracyclines into cardiotoxic substances. For this study, researchers examined the effects of variants in 2 CBR-producing genes, CBR1 and CBR3, on the risk of cardiomyopathy.

The case-control study compared 165 childhood cancer survivors who developed cardiomyopathy and 323 survivors with no heart disease. The patients were diagnosed between 1966 and 2008,with approximately 80% treated after 1981. The median age at the time of diagnosis was 7.5 years. Among patients treated with high doses (greater than 250 mg/m2), the patients predictably developed cardiomyopathy regardless of their genotype. However,among those patients who received lower doses, both CBR1 and CBR3 variants were found to increase the risk. Those with the CBR1 variant had a 5.3-fold increased risk of cardiomyopathy compared with patients carrying the low-risk variant, whereas patients with the CBR3 variant had a 3.1-fold increased risk.

With higher doses of anthracyclines, other unknown factors likely come into play in causing cardiomyopathy. Dr. Bhatia and colleagues are trying to determine these factors, in addition to finding other mechanisms thatmay contribute to heart disease occurring at low doses. “We're working to establish predictive models to develop preventive interventions in a prospective study with newly diagnosed patients,” she notes. That larger cohort studywill likely take another 4 to 5 years to complete. Dr. Bhatia hopes this model can be used to study other toxicity outcomes of pediatric cancer treatment, such as coronary artery disease and stroke.

The study has generated an enthusiastic response based on the possibilities it presents for a more personalized approach to preventing toxicities in pediatric cancer patients. “It's the first inkling that we can begin to do a better job in treatment ifwe can account for these unique differences on an individual or genetic basis,” says Melissa Hudson,MD, director of the cancer survivorship division at St. Jude Children's Research Hospital in Memphis, Tennessee. “I hope this moves forward quickly so we can begin to inform our therapeutic decisions more appropriately.”

Alternatives to anthracyclines are available, particularly for lower dose treatments. For patients with higher risk diseases, such as acute myelogenous leukemia and sarcoma, high-dose anthracyclines are the main form of chemotherapy used. In those cases, physicians would need to consider increased surveillance and pharmacological interventions to prevent heart damage, Dr. Bhatia notes.

Yoga Improves Sleep, Reduces Fatigue

A 4-week yoga programdesigned specifically for cancer survivors was found to improve sleep and reduce fatigue in what to the authors' knowledge is the largest randomized controlled study to date to examine the value of yoga in this population. “This study is a creative application of scientific technique to complementary medicine, and there are literally millions of patients who could benefit,” says ASCO President George Sledge, Jr, MD.

Few treatments for sleep problems and fatigue are effective in cancer survivors, notes lead author Karen Mustian, PhD, MPH, assistant professor of radiation oncology and community and preventive medicine at the University of Rochester Medical Center in Rochester, New York. Both conditions are common among cancer patients: approximately 80% report sleep problems during treatment and 65% continue to have problems after therapy is completed. This study provides hope that a low-cost, nonpharmacological therapy can improve quality of life in these patients.

The randomized, phase 2/3 trialwas conducted through the University of Rochester Cancer Center Community Clinical Oncology Program and 9 affiliates. The yoga program was assessed in 410 survivors of early stage cancers (96% of whom were women and 75% of whom were patients with breast cancer) who had received standard chemotherapy or radiotherapy between 2 to 22 months before enrolling in the study. They also needed to have had sleep disturbances qualifying as 3 or higher on a scale of 1 to 10. The patients received either their usual follow-up care or follow-up care along with a standardized, twice-weekly, 4-week yoga program that combined elements from both gentle Hatha yoga and restorative yoga.Patients learned various yoga postures as well as breathing exercises and mindfulness techniques that incorporate meditation, affirmations, and visualizations.

The 206 patients who practiced yoga reported greater sleep quality,less fatigue,and a better quality of life, whereas the control group of 204 patients reported an increased use of sleeping medication during the same period. Yoga patients reported a 22% improvement in sleep quality versus 12% in the control group. In addition, the group of patients studying yoga had less clinically impaired sleep than the control group (31% vs 16%) and less daytime sleepiness (29% vs 5%). The control group also increased sleep medication use by 5% whereas the yoga participants reduced their sleep medication use by 21% during the study period.

Furthermore,the yoga group reported a 42% reduction in fatigue, whereas the control group reported only a 12% reduction after 4 weeks. “We can't say at this point whether other forms of yoga, such as heated yoga or more rigorous techniques, also would mitigate side effects,” Dr. Mustian says.

Key Points

  • Childhood cancer survivors who carry a specific variant of the CBR gene were more likely to develop heart disease when receiving low doses of anthracyclines than their counterparts who did not have the gene variant.

  • A 4-week yoga program designed specifically for cancer patients was found to improve sleep and reduce fatigue. The yoga patients also were able to reduce their sleep medication use by 21%.

  • Older women with early stage breast cancer who undergo lumpectomy and receive tamoxifen can safely forego radiotherapy, according to a follow-up study.

Older Women with Early Stage Breast Cancer Can Avoid Radiotherapy

Physicians at Massachusetts General Hospital in Boston have found in a follow-up study that some women aged 70 years and older with early stage breast cancer can safely forego radiotherapy. Specifically, women who undergo lumpectomy and receive tamoxifen can avoid radiotherapy without significantly affecting their survival. The standard of care for these women with very small tumors that are estrogen receptor (ER)-positive and lymph node-negative has been lumpectomy plus radiotherapy. However, older women are less likely to have aggressive disease or to experience a disease recurrence than their younger counterparts. At the same time, results in earlier cohorts of this study with a shorter median follow-up indicated that the risk of disease recurrence without radiotherapy was only marginally higher, according to lead author Kevin Hughes, MD, surgical director of breast screening and codirector of the Avon Comprehensive Breast Evaluation Center at Massachusetts General Hospital.

“The benefits of radiation are small,” Dr. Hughes said, noting that this larger study confirms these results and suggests that tamoxifen may replace the need for radiotherapy.

Researchers randomly assigned 636 women aged 70 years and older with stage I, ER-positive, lymph node-negative breast cancer who had undergone a lumpectomy to receive either tamoxifen (319 women) or radiotherapy (317 women). After 10.5 years, the risk of breast cancer recurrence in the same breast was found to be lower among women who received tamoxifen plus radiotherapy (2%) compared with those who received tamoxifen alone (8%). However, there was virtually no difference noted between the 2 groups in terms of cancer-specific and overall survival.

“There were no other benefits of radiation—for example, no impact on breast preservation or distantmetastases,” Dr. Hughes adds. He also suspects the rate of disease recurrence would be even lower among these women today because of more precise surgery.