In Europe, approximately 70% of cervical cancer patients are cured by either surgery or chemotherapy. However, for the 30% who develop secondary cancer or their cancer recurs, there is a very poor outlook – conventional chemotherapy leads to tumor shrinkage in only approximately 20–30% of patients, and survival is usually less than 1 year.
Researchers at the Department of Cancer Studies and Molecular Medicine at the University of Leicester (UK) have been carrying out a Phase II study (CIRCCa) exploring the effect of the addition of the experimental drug cediranib to standard chemotherapy on tumor shrinkage and overall survival. The researchers compared two groups of patients with relapsed or metastatic cervical cancer who were given chemotherapy with carboplatin and paclitaxel combined with either cediranib (34 patients) or placebo (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 tumours,” explains study researcher Paul Symonds, of the Department of Cancer Studies and Molecular Medicine at the University of Leicester.
Results from the study show that those patients given cediranib displayed greater tumor shrinkage (66%) compared with those treated with placebo (42%). They also found that those given cediranib showed a statistically significant (although modest) increase in median progression-free survival (35 vs 30 weeks). Alongside these changes, side effects (particularly raised blood pressure and diarrhea) were increased in the group taking cediranib, and were treated with standard medication. Following 1 month of treatment, those in the cediranib group were more likely to show reduced levels of the VEGF receptor 2 in blood.
The authors emphasize the promise of targeting tumor blood supply as a method to increase the effectiveness of chemotherapy in cancer. Symonds commented: “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.”
Looking forward, the study is now looking to correlate response to chemotherapy with the fall in VEGF receptor levels in the blood, and is also looking at other tumor biomarkers that may have shown a reduction in response to cediranib.
Andres Poveda, Head of the Gynecological Oncology Clinic at Fundación Instituto Valenciano de Oncología, Valencia, Spain, commented on the positive advances that have been made in recent years with regard to the treatment of cervical cancer: ‘”For two decades, advances in treatment for patients with advanced cervical cancer had been slow and scarce,” he said. “Between 1989 and 2009, modifications of chemotherapy regimens resulted in an increased survival rate of just 4 months. Then the first study to include an antiangiogenic drug, bevacizumab, obtained spectacular results, offering a survival benefit of 4 months in one study – which is the equivalent to that obtained over the previous 20 years.”
“The FDA recently approved the use of bevacizumab as it completely changed clinical practice,” Poveda added. “We are now waiting for Phase III results to confirm the favorable predictions of this treatment with cediranib.”