Abstract
Objectives: Vandetanib (ZACTIMA™) is a once-daily oral agent that selectively targets RET, VEGFR and EGFR signalling pathways. Vandetanib 300 mg/day has previously demonstrated antitumour activity in patients with hereditary medullary thyroid cancer (MTC). This study investigated the efficacy of vandetanib 100 mg/day in patients with hereditary MTC (study code D4200C00068).
Methods: Eligible patients with unresectable, measurable, locally advanced or metastatic hereditary MTC received vandetanib 100 mg. Upon disease progression, eligible patients could enter post-progression treatment with vandetanib 300 mg until a withdrawal criterion was met. The primary objective was to assess the objective tumour response rate (RECIST).
Results: The study comprised 19 patients (13 male/6 female; median age 45 years), including 15 (79%) who had a confirmed RET germline mutation. As of 18 December 2007, 14 patients continued to receive vandetanib 100 mg, two patients had entered post-progression treatment with vandetanib 300 mg, and three patients had discontinued treatment (1 due to an adverse event, 1 withdrawal of consent, 1 death). Preliminary objective tumour assessments have demonstrated partial responses in two patients, stable disease ≥24 weeks in six patients and progressive disease in two patients, yielding an objective response rate of 10.5% (2/19) and a disease control rate of 42% (8/19).
Conclusions: These preliminary results suggest that vandetanib 100 mg also has activity in patients with hereditary MTC. This study has completed accrual and a final analysis will be performed in April 2008. ZACTIMA is a trademark of the AstraZeneca group of companies.