Cediranib added to chemotherapy improves progression-free survival in cervical cancer

For patients with cervical cancer that has recurred after treatment or has spread elsewhere in the body, adding the experimental drug cediranib to standard chemotherapy improves tumor shrinkage and adds a modest improvement in progression-free survival. These findings were reported at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.

In Europe, approximately 70% of patients with cervical cancer are cured by either surgery or chemoradiotherapy. Those patients with recurrent or secondary cancer have a very poor outlook. Only about 20% to 30% have tumor shrinkage after conventional chemotherapy, and survival is usually less than 1 year.

In the phase II CIRCCa trial, researchers compared two groups of patients with relapsed or metastatic cervical cancer given conventional chemotherapy with carboplatin and paclitaxel plus either cediranib (34 patients) or an identical looking placebo tablet (35 patients).

"Cervical cancers with a well-developed blood supply can have a particularly bad outcome. The experimental drug cediranib blocks the cell surface receptor VEGF, which stimulates the growth of new blood vessels to feed the growth of tumors," explained study researcher Paul Symonds, MD, of the Department Cancer Studies & Molecular Medicine at the University of Leicester, United Kingdom.

In the study, patients who received cediranib in addition to chemotherapy had greater tumor shrinkage than those treated by chemotherapy plus placebo (66% versus 42%). There was also a modest but statistically significant increase in median progression-free survival (35 versus 30 weeks). There was no statistically significant difference in median overall survival.

One month into treatment, VEGF receptor 2 levels in blood were more likely to be reduced in cediranib group (median change in log10 VEGFR-2 from baseline 0.036 versus 0.067).

Side effects, particularly elevated blood pressure and diarrhea, were increased in patients taking cediranib, and were managed with standard medication.

Targeting the tumor blood supply seems to be a promising way to increase the effectiveness of chemotherapy in cervical cancer, Symonds said. "Recurrent or metastatic cervix cancer is really difficult to treat with a low response rate and poor survival. This study has opened up a new avenue of investigation for a difficult-to-treat cancer."

The researchers are now conducting an individual patient analysis to correlate response to chemotherapy with the fall in VEGFR receptor levels in the blood. They are also looking at other tumor biomarkers that may have been reduced by cediranib.

Commenting on the study, Andres Poveda, MD, head of the Gynecological Oncology Clinic at Fundación Instituto Valenciano de Oncología, Valencia, Spain, who was not involved in the research, said the CIRCCa study is the second recent trial to show the benefit of adding an antiangiogenic drug to chemotherapy in cervical cancer.

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