A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer.

J Clin Endocrinol Metab 2012 Sep 6;97(9):3179-84. Epub 2012 Jul 6.

Division of Medical Oncology, Mayo Clinic Rochester, Rochester, Minnesota 55905, USA.

Context/objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC).

Design/setting/patients/interventions/outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response.

Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease.

Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC.

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Source
http://dx.doi.org/10.1210/jc.2012-1520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431569PMC
September 2012
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A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer.
Dowlati et al.
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J Clin Oncol 2008

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