In the United States, gynecologic cancers affect nearly 80,000 women annually and are the cause of death in more than 25,000 women.1
Cancers arising in the uterus are the most common, with 42,000 cases in 2009, followed by 21,500 cases of ovarian cancer, and 11,270 cases of cervical cancer.1
Although ovarian cancer is not the most common gynecologic cancer, it remains the most lethal. More women die each year from ovarian cancer than from uterine and cervical cancers combined.
Chemotherapy in the adjuvant setting is the standard of care for most gynecologic malignancies. For ovarian cancer, chemotherapy consists of a platinum and taxane. It is indicated in women with grade 3 stage IB or IC disease and in all women with a diagnosis of stage II disease or higher.2
In advanced uterine cancer, randomized trials have shown that chemotherapy is superior to radiation therapy in the adjuvant setting. Based on completed clinical trials, standard of care consists of a 3-drug combination of doxorubicin, cisplatin, and paclitaxel.3
This regimen, however, is associated with excessive toxicities, so most centers use carboplatin and paclitaxel in an alternative regimen. Recently, a randomized trial comparing these 2 treatments completed enrollment and results are eagerly anticipated.4
In cervical cancer, chemoradiation with cisplatin is a curative regimen in women with locally advanced disease and can be used as primary therapy in lieu of radical hysterectomy. A recent trial from South America compared chemoradiation with a combined approach of chemoradiation followed by systemic combination chemotherapy using cisplatin and gemcitabine (Gemzar).5
At the American Society of Clinical Oncology (ASCO) meeting in 2009, the study investigators reported that adjuvant systemic chemotherapy improved disease-free and overall survival in women with cervical cancer. This raises the possibility that adjuvant chemotherapy may someday play a larger role in the treatment of cervical cancer.
The use of adjuvant or first-line chemotherapy has led to improvement in survival outcomes for women with gynecologic cancers. Still, for those women who experience relapse, the disease is often incurable and most will likely succumb to it. While there are treatment options for recurrent gynecologic cancers, trials have generally focused on ovarian cancer, leaving it up to patients and their providers to extrapolate from the data how the treatments might apply to cervical or uterine cancers.A number of agents are approved to treat first or subsequent ovarian cancer relapses. In endometrial cancer, however, the US Food and Drug Administration has not approved any agent for second-line therapy. Thus, there is a desperate need to broaden options and improve the outcomes for women with recurrent disease. Several promising treatments are in development for gynecologic cancers.Bevacizumab (Avastin)
Bevacizumab is a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF)-alpha.6,7
It is approved for use in colorectal cancer, non–small cell lung cancer, and breast cancer. Recently completed trials indicate it may also be highly active in gynecologic cancers (Table 1
Burger and colleagues reported the results of Gynecologic Oncology Group (GOG) 170D, a phase II trial of bevacizumab in women with recurrent ovarian cancer.8
Eligible patients had measurable or assessable disease and had received up to 2 previous chemo-therapy regimens. Platinum-sensitive patients with a treatment-free interval of ≥12 months were required to have been re-treated with a platinum-based regimen. The study accrued 64 patients, of which 62 were evaluable. The overall response rate (ORR) was 21% (90% confidence interval [CI], 12.9%-31.3%), and 32 (52%) patients had stable disease as their best response. At 6-month follow-up, 40% had progression-free survival (PFS; 90% CI, 30%-53.6%). In this study, grade 3-4 gastrointestinal (GI) toxicity was rare, but 9.7% of patients developed grade 3-4 hypertension. Overall, toxicities were primarily grade 1-2. The most common adverse events were pain (50%), constitutional symptoms (45.6%), hepatic toxicity (33%), renal complications (30%), proteinuria (30%), anemia (30.6%), leukopenia (29%), hemorrhage (23%), diarrhea (21%), constipation (20%), coagulation problems (18%), nausea (15%), and hypertension (13%). While there were no reports of GI perforation in this study, a similar study conducted by Genentech was halted after 11% of participants experienced GI perforation.9
Prior treatment appeared to correlate with an increased risk of GI perforation; 24% of patients treated with 3 previous regimens experienced perforation, while no perforations occurred in patients who received ≤2 prior regimens.