NEW YORK CITY—The oral anabolic steroid oxandrolone can help cancer patients with involuntary weight loss to gain lean body mass, while improving their quality of life and performance status, a preliminary prospective study suggests.
“Oxandrolone appears not simply to increase weight in patients who often have severe disease-related cachexia, but also to help reverse the underlying pathology, improving metabolically active tissue compartments across the board,” said Jamie H. Von Roenn, MD, Professor of Medicine in the Division of Hematology/Oncology and Director of the Palliative Care & Home Hospice Program at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center there. “This, in turn, may result in improved function and quality of life.”
In the four-month study of 131 patients with cancer-related involuntary weight loss, all of whom took 10 milligrams of oxandrolone twice a day, 81% of patients either gained or maintained weight, Dr. Von Roenn reported. Of note, she added, was that lean tissue weight increased by an average of 7.5% at four months.
She spoke here last month at a news conference sponsored by Bio-Technology General Corp., which manufactures oxandrolone under the brand name Oxandrin.
Dr. Von Roenn reported data on the first 37 patients at the 2002 ASCO annual meeting, and a poster study about the final toxicity data on all 131 patients was presented at this year's meeting.
An Insidious Process
At diagnosis, up to 50% of cancer patients suffer from involuntary weight loss; as the disease advances, between 60% and 80% of patients are affected, depending on the tumor site, according to Dr. Von Roenn. Patients with solid tumors are most at risk, she said.
In the cancer patient, unintentional weight loss sets off an insidious process, she explained. Without intervention, proteins break down, muscles waste away, immune function is compromised, and the patient becomes weak. The risk of infections, including pneumonia and urinary tract infections, increases.
Meanwhile the patient starts to become depressed, and just getting out of bed becomes a chore. Compliance with medical therapy drops, as the patient is no longer able to tolerate the drugs. “Eventually the patient becomes bedridden, develops bed sores, and there's a predictable rise in mortality,” Dr. Von Roenn said.
The culprit is not the loss of body weight per se, but the loss of lean body mass, the site of 99% of the body's metabolic functions, Dr. Von Roenn said. Several studies have found that as many as one in five cancer patients die from loss of lean body mass, malnutrition, and its complications.
The Forgotten Vital Sign
Weight loss is a vital sign, just like blood pressure or temperature, she said. “But even the medical community often fails to recognize it as such. Often we don't get a patient's weight unless we specifically ask.”
Unintentional weight loss is not limited to the cancer patient, Dr. Von Roenn added. “Whether it's related to AIDS or chronic obstructive pulmonary disease or something else, the result is all the same.”
Even a 5% loss in total body weight will have an impact on prognosis, she said.
So why not just make the patient take in more calories?
Despite the appearance of malnutrition, the wasting syndrome associated with cancer is caused by the underlying disease process and is usually not reversible with improved nutrition, Dr. Von Roenn explained. Orally or parenterally administered nutrition frequently results in increased body fat, not increased lean body mass.
While necessary, “calories and protein alone are not sufficient to regain the lean tissue lost in the patient with involuntary weight loss associated with disease,” she said.
Other Pharmacological Options
As a result, physicians have turned to pharmacological options. But, said Dr. Von Roenn, none of the conventional therapies really meets the needs of patients with cancer cachexia.
Megestrol is an effective appetite stimulant, and its use has been associated with increased weight and an improved sense of well being in patients with cancer, she said. “But it doesn't increase lean body mass.”
Dronabinol, a marijuana derivative, has also been proven to have only a limited role, increasing appetite but not weight, she said. And dexamethasone has a very limited role, stimulating appetite for just four to eight weeks, after which its effects may diminish.
In fact, Dr. Von Roenn said, prolonged dexamethasone use has even been associated with wasting—in other words, it can exacerbate the very disease it is supposed to treat.
While oxandrolone has been indicated as an adjunctive therapy for weight gain for more than three decades, clinical trials for cancer cachexia are just starting to be performed.
The new study enrolled 131 patients with cancer cachexia whose average age was 68; 71 were men.
Most of the patients had solid tumors, and average weight at baseline was 134 pounds, with a range of 64 to 240 pounds. “You might ask, why would someone who weighs 240 pounds have to lose weight, but he had no lean body mass,” Dr. Von Roenn explained.
The study design included an integrated approach of oxandrolone—10 mg twice daily for four months, a resistance exercise program, and individualized nutritional recommendations. “All the patients were required to have adequate caloric intake,” she said.
By two months, body weight had increased an average of 2% and lean tissue weight an average of 4.1%, Dr. Von Roenn reported. By four months, body weight and lean tissue weight had increased by 3.5% and 7.5%, respectively.
While these numbers might not seem high, “you have to realize that without intervention, their weight would have continued to drop from baseline,” Dr. Von Roenn said.
Plus, “even if a patient's weight remained stable, they gained muscle and lost fat, so there was an improvement in metabolically active tissue compartments.”
Performance scores dropped from an average of 1.7 to 1.2, she said, with patients who lost the most weight showing the most benefit.
And quality of life, as measured by the 156-point Functional Assessment of Chronic Illness and Therapy scale, dropped from 81 to 17 at two months.
Oxandrolone Well Tolerated
Oxandrolone was very well tolerated, although one patient had to stop taking the drug due to elevated transaminases; levels went back to normal within two weeks. Nineteen percent of patients developed edema and 18% experienced dyspnea, the study showed.
One patient died within 24 hours of the first dose, “but there was no evidence the death was drug-related,” Dr. Von Roenn said.
Overall, the study revealed a non-clinically significant, 29% increase in transaminase levels, no change in bilirubin, a 36% drop in high-density lipoprotein (HDL) levels, and a 13% increase in low-density lipoprotein levels.
Also, oxandrolone did not stimulate tumor growth in nude mice orthotopically implanted with human tumors, Dr. Von Roenn said.
The drug is contraindicated in patients with cancers that have the potential to be stimulated by testosterone such as prostate and testicular, she noted.
Dr. Von Roenn noted that she is now conducting a placebo-controlled trial of oxandrolone in patients with cancer cachexia.
Also speaking at the news conference, Fred Sattler, MD, Chair of Infectious Disease and Professor of Medicine and Biokinesiology at the University of California's Keck School of Medicine in Los Angeles, said studies of oxandrolone in patients with wasting due to AIDS or chronic obstructive pulmonary disease have also proven the drug to have a good safety profile.
“While we consistently see a decrease in high-density lipoprotein, or good, cholesterol, HDL levels shoot back up to baseline when the drug is stopped,” he said. “And since oxandrolone is rarely given for more than four months, it's not a problem.”
While no one knows exactly how the drug works, oxandrolone is an anti-catabolic agent which. in the broadest sense, increases nitrogen retention, which correlates with an increase in lean body mass, Dr. Von Roenn said. “But we don't understand it at the cellular level.”
“Anabolic strategies such as oxandrolone and resistance exercise consistently increase total and lean body mass—regardless of the disease,” Dr. Sattler said.
“Sustaining weight and lean body muscle is a good thing,” he added. “We jumpstart patients with the anabolic androgen and then we can proceed to treat the underlying disease, whether it is cancer or HIV.”
One Patient's Story
Duane Carr, a 68-year-old cancer survivor who participated in the clinical trial, credited oxandrolone with giving him his life back.
“It gave me a second life,” he said at the news briefing. “It got me off the chair and onto my feet. Now I can do whatever I want, even ski.”
Mr. Carr, who lives outside of Burbank, CA, said cancer spread to his bone after being found in 26 of 27 removed lymph nodes. His weight dropped from 195 to 142 pounds. “I had no muscle, just flaccid tissue,” he said.
After just a week and a half on the drug, Mr. Carr said, he noticed a difference. “I could see some muscle,” he said. By three months, he had reached his desired weight of 162 pounds—“all muscle.” He said he experienced no side effects.
There were other positive changes as well, Mr. Carr said, including increased appetite and improved mental outlook.
“I'd recommend [oxandrolone] to any patient in similar circumstances,” he said.