Aug 24, 2012 - Phase II Trial Examines Cediranib as a Treatment for Mesothelioma
Researchers from the University of Chicago recently completed a Phase II clinical trial of Cediranib as a potential new treatment for malignant mesothelioma. Presented at the annual meeting of the American Society of Clinical Oncology, the research examined vascular endothelial growth factor (VEGF) and its response to Cediranib as a measurement of its effectiveness against mesothelioma.
VEGF is a key factor in the growth of cancerous mesothelioma tumors. VEGF directly correlates to the growth of new blood vessels both leading to and within mesothelioma tumors. Theoretically, by attacking VEGF scientists could effectively cripple mesothelioma. In previous research, a number of VEGF inhibitors have shown promise as anti-mesothelioma agents though none have proven to be curative agents.
The study was a collaborative effort between researchers at the University of Chicago, Princess Margaret Hospital at the University of Toronto, London Regional Cancer Program in Ontario, the University of California, the University of Southern California, Central Illinois Hem/Onc Center, and Oncology/Hematology Associates in Chicago.
Cediranib is an oral tyrosine kinase inhibitor of VEGF but had not been fully explored as a potential treatment option. The study selected participants diagnosed with malignant mesothelioma who had not undergone more than 1 regimen of chemotherapy. Eight-five percent of the patients were men, mostly falling between the ages of 44 and 81. Thirty percent of the patients were suffering from pleural mesothelioma while 70% had been diagnosed with peritoneal mesothelioma. Seventy-two percent had also been diagnosed with epithelial mesothelioma, the most treatable and most responsive to various mesothelioma therapies including drug therapy.
Orally administered daily, Cediranib was initially dosed at 45 mg orally daily but proved to be too toxic to the patient at those levels and was decreased to 30 mg daily. In order to accurately assess the effect of Cediranib on tumor growth, the patients were required to undergo CT scans every 28 days.
Though the researchers had held high hopes for this form of treatment, the results they observed fell in line with previous attempts to use VEGF inhibitors as treatment for various forms of mesothelioma. Ten percent of the participants expressed partial responses to the treatment while only 34% displayed “disease stability” (halting of tumor growth and disease progression) for a median period of just over 8 months. The remaining 66% of patients registered no response at all to the treatment.
Treatment with Cediranib at a 30 mg dosage daily was relatively toxic with roughly 30% of participants reporting adverse reactions and requiring cessation of treatment. Side effects included fatigue, hypertension (high blood pressure), diarrhea, hyponatremia (low blood sodium levels), thrombosis (blood clotting within veins or arteries), acute renal failure, heart arrhythmias and several other complications.
The scientists concluded that though Cediranib did display some anti-mesothelioma traits, treatment as far too risky to progress further. Still, the clinical trial was far from a failure. The team recorded significant data that VEGFs in general, though not Cediranib specifically, could indeed lead to a possible progression-free treatment for malignant mesothelioma.
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