IMATINIB MAY BE EFFECTIVE FOR REFRACTORY DESMOID TUMORS

NEW YORK (Reuters Health) Oct 08 - Imatinib (Gleevec) may be effective at controlling inoperable or difficult-to-resect desmoid tumors, according to a study reported October 1st in Clinical Cancer Research.

But the unpredictable nature of these tumors, coupled with a lack of any obvious molecular reason to account for imatinib's apparent impact, is for the moment keeping physicians from recommending the drug as a front-line treatment for advanced disease.

As part of an ongoing phase 2 trial of imatinib, researchers in the Sarcoma Alliance for Research through Collaboration (SARC) treated 51 patients with desmoid tumors (median age: 34 years). Depending on their body surface area, patients took either 100, 200, or 300 mg twice daily.

Most patients had at least a halt in disease progression while on imatinib. The rates of progression-free survival at 2, 4, 12 and 36 months were 94%, 88%, 66%, and 58%, respectively. In three patients (6%), tumors shrank by at least 30%. However, no correlation between drug efficacy and the molecular markers tested (including cKIT and the PDGF receptor, among others) could be identified to explain imatinib's activity.

"I think that we've proven this is a drug that can be used. It doesn't work for everyone but it works often enough that it's worth trying if a patient does have progressive tumor," said lead investigator Dr. Rashmi Chugh, Assistant Professor of Hematology/Oncology at the University of Michigan.

But, she added, imatinib is not necessarily her first-line therapy-of-choice. Other options include surgery, non-steroidal anti-inflammatory agents, tamoxifen, chemotherapy, and radiation. Ideally, she said, the tumors can be excised. If not, the goal is to make the disease chronic but manageable, like diabetes. Imatinib "is just another drug that we can incorporate into our care of these patients," she said.

Dr. Michael Heinrich of Oregon Health and Science University's Knight Cancer Institute, who was not involved in the study, said, "I would use it as a third-line or later therapy at this point."

"I think it's a totally open question as to how well (imatinib) works, and if it does work, how is it working," he said.

Dr. Heinrich, who published a smaller study of imatinib and desmoid tumors in 2006, pointed out that "in all other cancers for which imatinib is effective, there is an underlying mutation affecting an imatinib drug target protein that explains why imatinib works. Aggressive fibromatosis is the exception to this rule."

Yet, said Dr. Heinrich, neither his study nor the current one "really resolves the issue of how useful is Gleevec for this disease." That's because there is no normal course of the disease. It can be both indolent and aggressive, and it's difficult to know what would have happened had patients remained untreated. At times, Dr. Heinrich said, even aggressive disease can spontaneously stop growing for extended periods.

Also unanswered, he added, is imatinib's efficacy relative to other therapies, as the current study made no such comparisons.

"For patients who fail or refuse hormonal or low-dose chemotherapy treatment...it may be reasonable to consider imatinib therapy," the authors write. "For patients in need of rapid shrinkage of their tumor due to disabling symptoms or impending loss of limb or organ damage, aggressive chemotherapy may be preferable."

"Imatinib probably has a role in the treatment of aggressive fibromatosis, but further comparative studies are needed to determine the best treatment strategies," Dr. Heinrich concluded.

Clin Cancer Res. Posted October 1, 2010. Abstract