Anabolic agent and appetite stimulant improved weight gain, lean body mass

Oxandrolone and megestrol acetate improved self-reported anorectic symptoms and fatigue in chemotherapy patients with solid tumors.

“We think the complementary effects that the two agents have on appetite, overall weight gain and lean body mass suggest that their combination may result in optimal effects in a similar patient population,” Glenn Jay Lesser, MD, associate professor of Hematology and Oncology at the Wake Forest University Baptist Medical Center, said during his presentation at the 2008 ASCO Annual Meeting.

Lesser and colleagues randomly assigned 155 patients with solid tumors receiving chemotherapy to oxandrolone 10 mg twice daily (n=80) or megestrol acetate 800 mg per day (n=75) for 12 weeks.

“The primary objective was to compare the effects of both drugs on lean body mass and weight,” Lesser said.

After 12 weeks, the researchers reported changes in weight (oxandrolone: –3.4 lb. vs. megestrol acetate: +5.8 lbs.; P<.001) and fat mass (oxandrolone: –4.89 vs. megestrol acetate: +2.68; P<.001) in both treatment arms.

Oxandrolone demonstrated a trend toward increased lean body mass, compared with megestrol acetate, but was not statistically significant (+2.6 vs. +0.8).

Though global quality of life and fatigue remained statistically unaffected by either treatment, researchers reported improvement on the anorexia/cachexia subscale (oxandrolone: 6.7 vs. megestrol acetate: 11.3; P=.01).

“Both treatment arms experienced improvement in self-reported anorectic symptoms and both arms experienced modest improvement in self-reported fatigue after 12 weeks of treatment,” Lesser said. –by Stacey L. Adams

We are looking for answers to the call from WHO and the multiple documents from the Institute of Medicine, to integrate palliative care and symptom management into cancer care — from diagnosis throughout the trajectory of disease. Evidence based on our understanding of the pathogenesis of symptoms and on results from phase-3 clinical trials are essential for the development of optimal palliative cancer care.

This is a well- designed and well-implemented phase-3 trial testing the effectiveness of a potent appetite stimulant vs. an anabolic agent for the treatment of involuntary weight loss in patients with cancer. Unfortunately, the oncology community often sees weight loss as an expected and untreatable event for patients with advanced cancer. In the past, trials evaluating therapy for patients with cancer cachexia have enrolled a very late stage population by requiring weight loss of greater than or equal to 10% of pre-illness weight for enrollment. I applaud these investigators for their efforts to enroll patients earlier in the course of their illness, requiring only a <5% or <3% weight loss for enrollment.

It appears, not only from this study, but from previous trials (particularly in the setting of HIV wasting), that an anabolic stimulus is important for the treatment of wasting. For patients with cancer-related weight loss, the disproportionate loss of muscle mass compared to fat mass supports this contention. Currently available pharmacologic therapies are unlikely to reverse cancer-related involuntary weight loss. As with many of the symptoms we are working to ameliorate, advances in treatment will most likely result from targeted therapy based on a better understanding of the biologic basis of symptoms.

– Jamie H. Von Roenn, MD

Professor of Medicine in the Division of Hematology/Oncology,

Feinberg School of Medicine at Northwestern University,

Robert H. Lurie Comprehensive Cancer Center