Roxanne Nelson

November 18, 2011

November 18, 2011 (Cleveland, Ohio) — Glucosamine combined with chondroitin might improve arthralgias induced by aromatase inhibitors. An early-phase study showed that the combined use of these agents conferred a benefit in breast cancer patients experiencing joint pain and stiffness related to the use of aromatase inhibitors.

Improvements were observed on several measurement scales, according to the data presented here at the 8th International Conference of the Society for Integrative Oncology.

Aromatase inhibitors are widely used in the treatment of breast cancer but are associated with significant musculoskeletal adverse effects, including joint pain and stiffness. "We know that these symptoms are unresponsive to conventional pain medication and often lead to low adherence to aromatase inhibitor therapy," said lead author Heather Greenlee, ND, PhD, assistant professor of epidemiology and medical oncology at Columbia University in New York City.

"Women who don't adhere to the treatment do not attain the survival benefit," she explained.

Mixed Results

In 2002, a meta-analysis suggested that glucosamine and chondroitin might be effective in relieving pain and disability in osteoarthritis, Dr. Greenlee noted. However, in 2006, the publication of a major randomized trial — the GAIT study — showed that glucosamine and chondroitin, alone and in combination, were not effective after 6 months, especially for treating osteoarthritis.

Despite the negative results, a subgroup analysis did suggest there was a benefit with glucosamine plus chondroitin in patients with moderate to severe pain at baseline.

"Around the time that the results were published, we had been planning on doing this study," she told meeting attendees. "We were trying to decide if this stopped us in our tracks" — whether or not we should go forward to see if this could benefit our patients.

Improvements Observed

Dr. Greenlee and colleagues decided to move forward, and received funding from AstraZeneca to conduct a study. In this phase 2 single-group trial, the researchers evaluated whether they could detect any benefit with glucosamine plus chondroitin in this patient population.

The cohort consisted of postmenopausal breast cancer patents with stage I to III disease who had been on aromatase therapy for at least 3 months, who reported a pain rating of 4 or higher on a 10-point visual analog scale, and whose pain worsened after initiating treatment with aromatase inhibitors if they had preexisting osteoarthritis.

Initially, 53 women were enrolled, but 16 dropped out for various reasons, Dr. Greenlee explained. The study had 2 main end points at 12 and 24 weeks; 40 women completed 12 weeks of the trial, and 37 completed the entire study.

The treatment population was diverse — about 40% white and 40% Hispanic, she pointed out. The median patient age was 61 years. The study participants were generally well educated, tended to be overweight, and were, on average, about 3.5 years postdiagnosis.

"It is important to note that nearly all of the women were on [anastrozole], and the study was conducted before any of the aromatase inhibitors went generic," she said. "It is also important to note that the people who participated in this study were very interested in the use of complementary modalities."

Participants took 1500 mg/day of glucosamine and 1200 mg/day of chondroitin, and were evaluated every 6 weeks at the clinic. The primary end point of the study was change in the Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARS) criteria at 24 weeks.

Secondary end points included changes in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH), and Brief Pain/Stiffness Inventory-Short Form (BPI-SF). The visual analog versions of the WOMAC and the M-SACRAH were used for this study (range, 0 to 100 mm), where a higher score reflects a worse outcome.

"OMERACT-OARS was the primary outcome in the GAIT study, and we wanted to model our study on the way the GAIT study was designed," Dr. Greenlee explained.

There was a drop in pain and stiffness in the hips and knees at 12 and 24 weeks, as well as improvement in function. "This affected about 50% of the women," she explained. "We saw a very similar pattern looking at the hands and the wrist. We saw similar results with the Brief Pain/Stiffness Inventory — with about 35% to 50% of women."

She pointed out that they also wanted an objective measure of any change, so they tested women with the Martin Pneumatic Squeeze Dynamometer, which is a grip strength bulb. Over the course of the study, women strengthened their grip strength on 3 different measures.

For the primary end point, the women have to meet 1 of 2 parts of the criteria, explained Dr. Greenlee. They have to either have an improvement of 50% or greater on one of the function scales, including a 10% change on the global assessment scale, or a 20% or more improvement on the pain and function scale and a significant change in the global assessment scale.

At 12 weeks, 38% of women met these criteria; at 24 weeks, about 46% of women met the criteria. "We said in our protocol that if 50% or more of these women met the criteria, we would go on with a subsequent study," she said. "We are right on the borderline, so we are trying to decide what to do."

For the secondary end points, there was significant improvement in the mean WOMAC score at 24 weeks, compared with baseline, in both the function domain (mean difference, 11.9 mm; P = .01) and the pain domain (mean difference, 10.7 mm; P = .02). However, a significant improvement was not observed in the stiffness domain (mean difference, 7.5 mm; P = .15).

The M-SACRAH scale showed results similar to those observed on the WOMAC scale. There was a significant improvement in function at 24 weeks (mean difference, 8.4 mm; P = .02) and in the pain domain (mean difference, 12.9 mm; P < .01), but no significant improvement in stiffness (mean difference 7.9 mm; P = .13).

The most common adverse effects reported were headache, dyspepsia, and nausea.

"Glucosamine and chondroitin appear to be safe in women with breast cancer, and may confer a benefit for aromatase-inhibitor-induced pain," concluded Dr. Greenlee. "We're not sure if OMERACT-OARS is the best end point for studies like this, and we're considering pursuing this as a future study."

Gary Deng, MD, president of the Society of Integrative Oncology, doesn't see the mild improvements observed in this study, or in other trials looking at complementary modalities, as necessarily being a negative. "We always have to look at risk vs benefit," he told Medscape Medical News. "If an intervention is low risk, you may have a lower threshold of effect size. But even in chemotherapy, some of the effect size is not that great. In some cases, it may only be 5% or 10%, or extend life by just a few months."

"We have to keep things in perspective and not only make an evidence-based clinical decision; a lot of the time, we have to make a judgment call and look at the patient as a whole," Dr. Deng added, "and take into account what's important to them."

The study was funded by AstraZeneca.

8th International Conference of the Society for Integrative Oncology: Abstract 4. Presented November 10, 2011.

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