Yttrium-labeled somatostatin shows promise in thyroid cancer therapy

June 22, 2009

Receptor-targeted radiotherapy using yttrium-90 DOTA-Tyr3 octreotide could become a life-saving option for patients with iodine-refractory thyroid cancer, based on results from a phase II clinical trial.

Receptor-targeted radiotherapy using yttrium-90 DOTA-Tyr3 octreotide could become a life-saving option for patients with iodine-refractory thyroid cancer, based on results from a phase II clinical trial.

Blasting cancer cells with deadly beta-particles emitted by targeted Y-90 could fill a troubling gap in treatment options available to thyroid cancer, according to senior investigator Dr. Martin A. Walter, a research associate at the Institute of Nuclear Medicine in the University Hospital of Basel in Switzerland. No systemic therapy has proved effective for thyroid cancer that has turned refractory to iodine radiotherapy.

Metastases that cause symptoms, such as respiratory or swallowing problems, can be surgically removed. Chemotherapy, on the other hand, is highly toxic and largely ineffective, he said.

Results from the Basel phase II trial, however, could raise hopes among oncology and imaging specialists, said Walter, who is also a nuclear medicine physician at the David Geffen School of Medicine, University of California, Los Angeles.

"With Y-90 DOTA-TOC, physicians now have an additional tool for thyroid cancer in case of dedifferentiation and loss of iodine avidity," Walter told Diagnostic Imaging.

Walter and colleagues enrolled 24 patients with iodine-refractory thyroid cancer who underwent a median cumulative dose of 13 GBq Y-90 DOTA-TOC radiotherapy. The investigators assessed biochemical response, survival, and long-term safety of the procedure using National Cancer Institute criteria. They found that those patients who responded to treatment had longer survival rates.

They published results in the May issue of Cancer.

Seven patients (29.2%) showed response to therapy, while eight (33.3%) developed hematologic toxicity grade 1-3, and four (16.7%) developed renal toxicity grade 1-4. Median survival was 33.4 months from time of diagnosis and 16.8 months from time of first treatment. The correlation between response to treatment and survival was statistically significant (p = 0.04).

According to the clinical literature, management of thyroid carcinomas includes thyroidectomy, iodine radiotherapy, and suppressive thyroid hormone replacement. Unfortunately, many tumors become refractory and prognosis turns bleak after progressive dedifferentiation.

If proven successful in further studies, Y-90 DOTA-TOC could provide a welcome alternative. It could also be complemented with radiosensitizing drugs such as gemcitabine or tyrosine kinase inhibitors, which also show promising results in thyroid cancers, said Walter, whose research group is already fine-tuning protocols for the next trial.

"We will intensify treatment by increasing the number of treatment cycles and the therapeutic dose," he said.