A phase II trial of doxorubicin and interferon alpha 2b in advanced, non-medullary thyroid cancer

Background: The combination of doxorubicin and interferon alpha is supported by preclinical data. We sought to evaluate the efficacy of this combination in patients with advanced thyroid cancer. Patients and methods: Patients with locally recurrent or metastatic, radioiodine- refractory thyroid cancer, excluding medullary carcinoma, were treated with interferon alpha-2b 12 million units/m(2) subcutaneously on days 1-5 and doxorubicin 40 mg/m(2) intravenously, on day 3, every 28 days. Results: 17 patients, 15 with well differentiated and 2 with anaplastic thyroid carcinoma, were enrolled; median age was 69 years. Three patients had received radiation plus low dose doxorubicin previously. In 16 patients assessable for response, 1 patient (6%), who had follicular carcinoma, achieved a partial response and 10 patients (62.5%) stable disease as best response. Median time to progression was 5.9 months and median overall survival 26.4 months. In 14 evaluable patients, 5 (36%) had a thyroglobulin response (30% or more reduction in serum levels). Grade 3/4 neutropenia occurred in 76% of patients and neutropenic fever in 24%. Other grade 3/4 adverse events included fatigue (41%), rigors (18%), fever (6%), nausea/vomiting (29%), anorexia (29%), stomatitis (24%), vision disturbances (18%), neuropathy (18%), and hyponatremia (6%). One patient developed heart failure. Conclusions: Doxorubicin and interferon alpha was associated with considerable toxicities but modest antitumor activity in patients with advanced, non-medullary thyroid cancer.