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Oral glutamine curbs radiation dermatitis in breast cancer patients.

SAN ANTONIO -- Oral glutamine appears to be a safe and effective way to reduce the cutaneous morbidity of radiotherapy in women undergoing breast-conserving surgery, V. Suzanne Klimberg, M.D., reported at the annual breast cancer symposium sponsored by the Cancer Therapy and Research Center.

In contrast, an aloe-based cream proved to be of no benefit for this purpose in a separate phase III clinical trial presented at the meeting.

Cosmetic outcomes in patients undergoing breast-conserving therapy are often limited by radiation injury to the skin and surrounding tissues, which can unpredictably be quite severe.

Based upon animal studies showing that glutamine reduced both acute and chronic radiation injury to the small bowel, Dr. Klimberg and her coinvestigators at the University of Arkansas for Medical Sciences, Little Rock, mounted a clinical trial in which 17 breast cancer patients were randomized to 30 g per day of oral glutamine or placebo beginning 1 week prior to starting radiotherapy as part of breast-conserving therapy and lasting until 1 week after radiation treatments ended.

The women were followed weekly for 7 weeks, then every 3 months for 2 years. Skin morbidity was rated using the Radiation Therapy Oncology Group's 0-4 scale. In this scoring system, 0 is no change, 4 is necrosis, and a score of 2 is assigned for moist desquamation, which is deemed unacceptable morbidity and a treatment failure.

The average score in the glutamine-treated group was 0.9, significantly better than the 1.4 in the placebo group. Only four of nine patients in the glutamine group scored a 2 during the first 7 weeks, whereas all eight patients in the placebo group did. None of the glutamine-treated patients scored a 3 and/or required a treatment delay because of radiation dermatitis, but three of eight patients in the placebo arm did.

At 1 year, three patients in the placebo group required narcotics for breast pain. Six of eight had significant breast edema, and four had markedly increased density of the treated breast. In contrast, while two women in the glutamine group reported mild pain, no one in the glutamine group required narcotics. None of the glutamine-treated patients had breast edema, and only one developed minimally increased breast density.

The mean cosmetic score in the glutamine group was 9.2, corresponding to "excellent," while in the placebo arm it was 7.3, which meant "fair to good."

Two patients in the placebo arm had local recurrences within 2 years. There were no local recurrences in the glutamine group.

In animal studies, oral glutamine doubles intracellular glutathione levels in normal breast tissue while depleting glutathione in breast tumors, resulting in increased apoptosis. This may not only account for glutamine's ability to reduce radiation morbidity to the breast, but it also raises the possibility that glutamine might enhance treatment efficacy as suggested by the lack of local recurrences in the pilot study, Dr. Klimberg said.

She and her colleagues identified a previously undescribed 9.3-kDa serum protein marker whose levels rose during glutamine therapy and fell back to basal levels upon treatment discontinuation. They are now attempting to characterize this potential biomarker more specifically, and to learn if its behavior predicts cosmetic outcome.

In a separate presentation, Donna L. Hoopfer, Ph.D., reported on 237 patients undergoing radiation therapy for nonmetastatic breast cancer who were randomized to thrice-daily application of an aloe cream, the vehicle cream, or baby powder during and for 1 month after radiotherapy. The aloe cream was formulated by the investigators specifically for this study using fresh aloe leaves.

There were no significant differences in skin pain, itching, dryness, or burning between the three study arms in this trial, which was funded by the Canadian Breast Cancer Foundation, said Dr. Hoopfer of the Cross Cancer Institute, Edmonton, Alta.
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Title Annotation:Women's Health
Publication:Internal Medicine News
Geographic Code:1USA
Date:Mar 1, 2005
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