Phase II trial of sorafenib (bay 43–9006) in patients with advanced anaplastic carcinoma of the thyroid (ATC)

Abstract

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is >20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]

Anaplastic Thyroid Cancer: A Review of Epidemiology, Pathogenesis, and Treatment

“…Median duration of PD/SD was 5.1 months, and median duration of survival was 3.5 months. This study is ongoing at this time [ 64 ].…”

Complete Remission of Anaplastic Thyroid Carcinoma after Concomitant Treatment with Docetaxel and Radiotherapy

“…On the other hand, targeted biological agents including antiangiogenic agents and tyrosine kinase inhibitors might represent a viable therapeutic option. Axitinib [ 10 ], combretastatin A4 [ 11 ], sorafenib [ 12 ], and imatinib [ 13 ] have been tested in small clinical trials of ATC, with a promising disease control rate ranging from 33% to 75%. However, these findings have been derived from limited number of the patients.…”

Thyroid Cancer: Molecular Aspects and New Therapeutic Strategies

“…Of the 15 evaluable patients, 2 (13%) showed an objective radiological response that was maintained for a median of 5.3 months. The most frequently observed grade 3 and 4 adverse events were lymphopenia (31%), skin rash (12%), weight loss (12%), and chest pain (12%) [ 39 ].…”