Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced anaplastic thyroid carcinoma (ATC)

Abstract

5580 Background: CA4P is the first tubulin-binding vascular disrupting agent tested in the clinic. Phase I studies were devoid of significant myelosuppression, DLT included cardiovascular side effects, and there was demonstrable activity in ATC (Cancer Res 2002; 62:3408; Clin Cancer Res 2004; 10:96). Methods: Patients with metastatic ATC, good performance status, normal ECG and cardiac function, and no prior therapy for disseminated disease were eligible for study. CA4P at a dose of 45 mg/m2 was administered as 10-minute IV infusion on days 1, 8 and 15 every 28 days (1 cycle) until progression of disease. Results: A total of 18 patients (pts) (11M/7F), median age 62 (range 40–71 yrs), received a total of 55.67 cycles of treatment. Therapy was well tolerated with mild to moderate nausea, vomiting, headache, and tumor pain (3 pts with grade 3) all of which essentially resolved within first 24 hrs. There was no clinically meaningful myelosuppression or cardiac toxicity. No objective responses were seen; 6 pts with stable disease and 12 pts progressed. Median progression free survival (PFS) was 7.4 wks (range 2–84+ wks); with 28% of pts progression free > 3.0 mos. (12.0+, 14.3, 15.3, 25.6 and 84.0+ wks). Pts without bulky disease tended to do better. Fourteen pts have died; 4 are alive; and 2 are alive and on-study at 12.0+ and 84.0+ wks. Median survival is on the order of approximately 20 wks. Conclusions: Approximately a quarter of patients treated with single-agent CA4P experience greater than 3 mos. freedom from progression. Combined modality strategies with CA4P and either chemotherapy and other targeted agents or with radiation are warranted. [Supported in part by a clinical grant from OXiGENE, Inc., Waltham, MA and NIH grant nos. M01 RR-00080]. No significant financial relationships to disclose.