Ovarian cancer is the seventh most common cancer in women worldwide, with an annual incidence of about 6.3 cases per 100,000 women, and an annual mortality rate of 3.8 per 100,000 women. Standard treatment of advanced ovarian cancer usually involves surgery, to remove as much of the cancer as possible ('debulking'), and platinum-based chemotherapy, with or without the addition of a taxane. However, despite good initial responses to platinum agents and taxanes, most women have disease relapse, require further treatment with chemotherapy, and eventually develop resistance to conventional chemotherapy drugs.
Many researchers are trying to find new drugs, which target different pathways, in order to treat ovarian cancer that has become resistant to standard chemotherapy. One target is the pathway for angiogenesis: the growth of new blood vessels. Although new blood vessels can form as part of the body's normal processes, cancers are especially reliant on angiogenesis, as they need a blood supply in order to grow. It is hoped that drugs that act to inhibit the growth of new blood vessels will slow or stop the progression of the cancer.
In this review we found evidence from five studies, comparing drugs which inhibit angiogenesis against either standard chemotherapy (carboplatin + paclitaxel) or placebo.
Two trials looked at the effect of adding bevacizumab to conventional chemotherapy in women who had just been diagnosed with ovarian cancer and had debulking surgery. Bevacizumab was given both alongside the chemotherapy, and then continued afterwards (called maintenance therapy). Taking the results of these two trials together, there was no significant benefit from adding bevacizumab to standard chemotherapy in terms of survival time, but there was fairly strong evidence that it might slow the growth of the cancer (increased progression-free survival (PFS)). However, the trials also showed that there were worse side effects in women who received bevacizumab in addition to chemotherapy (particularly high blood pressure, serious bowel problems and bleeding). One of these two trials also looked at the effect of giving bevacizumab concurrently with chemotherapy (not continuing afterwards), and found no significant improvement in either survival time or slowing cancer growth, but did find a significant increase in moderate and severe high blood pressure (hypertension).
A third trial looked at adding a different agent, AMG 386, to paclitaxel chemotherapy in women with recurrent ovarian cancer. The trial compared the addition of either a higher or lower dose of AMG 386 to placebo. It found no improvement in survival with either the higher or lower dose of AMG 386, but there were suggestions that it might slow cancer growth. It did not seem to increase side effects.
We identified two other trials; one comparing placebo to BIBF 1120, and the other comparing placebo to VEGF (vascular endothelial growth factor)-Trap. Neither study found evidence of slowing cancer growth/prolonging survival, or worsening side effects. However, these were both relatively small studies, which made them less likely to detect an effect that may or may not have been present.
All of the included trials that we identified reported only preliminary results, which had been presented at conferences, but not yet published in full. It is thus difficult to be sure of the specific details of how these trials were performed, and therefore to assess their risk of bias. We found 12 other on-going studies that fulfilled our inclusion criteria, and some of these are expected to release preliminary results soon.