MELOXICAM FOR EXTRAABDOMINAL DESMOID TUMORS

January 5, 2010 — Meloxicam (Mobic), a cyclooxygenase (COX)-2 inhibitor drug used for arthritis, has shown promise as a treatment for extraabdominal desmoid tumors, according to the results of a small pilot study.

The study results, which were published online December 21 in the Journal of Clinical Oncology, showed that of 20 patients treated with meloxicam who were available for evaluation, 19 (95%) had a final status of stable disease or better.

Extraabdominal desmoid tumors are generally sporadic in nature and can occur in virtually any body site, note the authors. However, they are primarily found in the extremities, chest, abdominal wall, and neck. They can be locally aggressive and invasive to surrounding anatomic structures, leading to pain, functional impairment, and deformity.

Management usually involves a multidisciplinary approach that includes surgery and radiation, but these have potential associated morbidities. This has led to investigations of both cytotoxic and noncytotoxic chemotherapy, but because the tumors are rarely fatal, finding a pharmacologic treatment with fewer complications is desirable, according to the authors.

"We recommend meloxicam for patients with extraabdominal desmoid tumors, instead of surgery first," said lead author Yoshihiro Nishida, MD, PhD, from the Department of Orthopedic Surgery at Nagoya University Graduate School of Medicine in Japan.

"However, our study included only a small number of patients, so if tumors do not respond to meloxicam treatment, we would then use surgery or other modalities such as radiotherapy or chemotherapy," he told Medscape Oncology.

Meloxicam Induced Responses, Well Tolerated

The authors hypothesized, on the basis of previous studies, that COX-2 might be a potential therapeutic target. Experimental in vitro and in vivo research demonstrated decreased cell proliferation in desmoid cell cultures and small tumors when COX-2 was blockaded with pharmacologic agents.

In this study, between 1991 and 2003, Dr. Nishida and colleagues identified 30 patients who were surgically treated for extraabdominal desmoid tumors at their institutions (excluding those with intraabdominal, familial adenomatous polyposis-associated, and unresectable tumors). Because of the high rate of relapse after surgery (53%), 22 patients have been prospectively treated with meloxicam since 2003.

None of the 22 patients had a known history of gastrointestinal disorders, such as gastritis or gastric ulcer, and no one in the cohort was receiving hormonal medications. Baseline imaging of desmoid tumors by magnetic resonance imaging (MRI) was obtained prior to beginning treatment with oral meloxicam 10 mg/day.

Patients were followed with physical examinations and MRI and/or computed tomography every 3 to 6 months, and meloxicam was administered for a median of 20 months (range, 3 to 66 months). Of this group of 22, 2 patients discontinued treatment because of adverse events and were not included in the final evaluation.

Among the 20 patients evaluated, the researchers observed 1 complete response, 7 partial responses, 11 patients with stable disease, and 1 patient who had progressive disease. Although the 2 patients who discontinued treatment were not included in the evaluation, they had stable disease at the time they stopped the therapy. Patient sex, tumor size, tumor site, follow-up interval, and period of medication were not significant prognostic factors of responsiveness. However, age appeared to play a role; good responders were significantly older than poor responders (P = .0091).

Meloxicam was well tolerated and none of the patients in the final analysis experienced any adverse effects. Of the 2 patients who discontinued treatment, 1 did so because of mild gastritis, and the other was elderly with had a history of cerebral infarction and suffered from intermittent pneumonia and diarrhea.

Surgery remains the mainstay for resectable sporadic desmoid tumors, especially extraabdominal ones, the authors write, and there is growing evidence that chemotherapy might be effective in managing life-threatening intraabdominal desmoid tumors. "However, the significant morbidity of aggressive chemotherapy should be avoided in patients with extraabdominal desmoids tumors," they say.

The authors point out that this was a prospective and consecutive-case–control study with a small number of patients. Even though 95% of the patients achieved stable disease or better, they note that they still cannot conclude that these results were "solely attributable to the meloxicam itself."

However, they add that it was crucial to prove that meloxicam had potential for treating extraabdominal desmoid tumors before undergoing a large placebo-controlled trial.

Further investigations are needed, but on the basis of these results, the authors recommend "meloxicam as the initial treatment for patients with extraabdominal desmoid tumors."

Unfortunately, these results cannot be extrapolated to children. "In the pediatric population, a pilot study is necessary," said Dr. Nishida. "Currently, we do not recommend meloxicam treatment for pediatric patients with extraabdominal desmoids tumors."

The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online December 21, 2009. Abstract