Inhibition of angiogenesis with drugs such as bevacizumab demonstrated activity and benefit in women with recurrent ovarian cancer. There is evidence in other tumor types such as breast cancer and colon cancer that the addition of bevacizumab to chemotherapy increases response rates, progression-free survival, and survival in some studies (222–224). Two large randomized trials (GOG 218 and ICON7) investigating the impact of the addition of bevacizumab to standard carboplatin and paclitaxel in patients with advanced ovarian cancer were completed (225,226). GOG 218 is a phase III three-arm randomized double-blind placebo-controlled trial. Patients in arm one received six cycles of carboplatin and paclitaxel and placebo starting with the second cycle and continuing for 16 additional cycles after the completion of chemotherapy. Patients in arm two received six cycles of chemotherapy with bevacizumab starting with cycle two and administered with chemotherapy followed by 16 cycles of placebo, and in arm three patients received bevacizumab starting with cycle two of chemotherapy and then received 16 additional cycles after the completion of chemotherapy. This study was designed to investigate the benefit of bevacizumab in combination with chemotherapy and as a maintenance therapy. The bevacizumab was administered at a does of 15 mg/kg, starting with the second cycle of chemotherapy, to decrease the risk of gastrointestinal perforation, which is a rare complication of this agent in the setting of its use in colorectal cancer. The results of GOG 218 reported a modest improvement of 3.8 months in progression-free survival in patients randomized to receive bevacizumab in combination with carboplatin and paclitaxel every 3 weeks and then as a maintenance therapy every 3 weeks for an additional 16 cycles for a total of 15 months’ treatment (225). The toxicity of bevacizumab was acceptable and the risk of bowel perforation very low (below 2%). The study did not find any improvement in overall survival, but follow-up is required. The ICON7 study is similar to the GOG study, although it is a two-arm study of carboplatin and paclitaxel plus or minus bevacizumab 7.5 mg/kg administered every 3 weeks with chemotherapy for six cycles and then as maintenance therapy for 12 additional cycles. The ICON7 results were presented and reported a statistically significant, yet modest, 1.7-month improvement in median progression-free survival in the experimental arm (226). The results of these studies support a role of bevacizumab in combination with chemotherapy in patients with advanced ovarian cancer. However, the cost of bevacizumab is very high and the improvement in progressive-free survival is short.
For the treatment of advanced-stage epithelial ovarian cancer, the following is recommended (Table 37.4):
Combination chemotherapy or intravenous carboplatin and paclitaxel or intraperitoneal cisplatin and paclitaxel (using the GOG 172 protocol) are the treatments of choice for patients with advanced disease. The advantages and disadvantages of the intravenous versus intraperitoneal routes of administration of these drugs should be discussed with the patient.
The recommended doses and schedule for intravenous chemotherapy are: carboplatin (starting dose AUC = 5–6), and paclitaxel (175 mg/m2), every 3 weeks for six to eight cycles, or the dose-dense regimen of carboplatin AUC 6 every 3 weeks for six cycles and weekly paclitaxel 80 mg/m2 (217).