Chapter 093. Gynecologic Malignancies (Part 4) pps

Chapter 093. Gynecologic Malignancies (Part 4) Patients with stage I disease, no residual tumor, and well or moderately differentiated tumors need no adjuvant therapy after definitive surgery, and 5-year survival exceeds 95%. For all other patients with early disease and those stage I patients with poor prognosis histologic grade, adjuvant platinum-based therapy is warranted. Large prospective randomized trials have demonstrated that adjuvant therapy improves disease-free and overall survival by 8% (82% vs. 74%, p = .008). For patients with advanced (stage III) disease but with limited or no residual disease after definitive cytoreductive surgery (about half of all stage III patients), the primary therapy is platinum-based combination chemotherapy. Approximately 70% of women respond to initial combination chemotherapy, and 40–50% have a complete regression of disease. Unfortunately, only about half of these patients are free of disease if surgically restaged. Although a variety of combinations are active, a randomized prospective trial of paclitaxel and cisplatin compared to paclitaxel and carboplatin in patients with optimally resected advanced disease demonstrated equivalent disease-free and overall survivals but with significantly reduced toxicity with the carboplatin combination. This regimen of paclitaxel, 175 mg/m 2 by 3-h infusion, and carboplatin, dosed to an AUC (area under the curve) of 7.5, is the preferred treatment choice for patients with previously untreated advanced-stage disease. Three randomized trials using intraperitoneal (IP) chemotherapy have demonstrated improved disease-free and overall survival compared to the intravenous administration of the same drugs. However, the increased toxicity (neuropathy, nephropathy, and catheter complications) is significant, and only about 40% of patients were able to receive full courses of therapy. Furthermore, the optimal dose and schedule of IP therapy has not been established, nor have any of the IP regimens been prospectively compared to the standard intravenous carboplatin-paclitaxel regimen. The ultimate role of IP therapy in the treatment of advanced ovarian cancer is unresolved. Patients with advanced disease (stages III and IV) and bulky residual tumor are generally treated with intravenous paclitaxel-platinum combination, and while the overall prognosis is poorer, 5-year survival may reach 15–20%. Historically, patients who had an excellent initial response to chemotherapy and no clinical evidence of disease had a second-look laparotomy. The second- look surgical procedure itself does not prolong overall survival, and outside of clinical trials its routine use is no longer recommended. Maintenance therapy may extend progression-free survival but has not improved overall survival. Patients with advanced disease whose disease recurs after initial treatment are usually not curable but may benefit significantly from limited surgery to relieve intestinal obstruction, localized radiation therapy to relieve pressure or pain from mass lesions or metastasis, or palliative chemotherapy. The selection of chemotherapy for palliation depends on the initial regimen and evidence of drug resistance. Patients who had a complete regression of disease lasting ≥6 months often respond to reinduction with the same agents; patients relapsing within the first 6 months of initial therapy rarely do. Progestational agents, tamoxifen, or aromatase inhibitors produce responses in 5–15% of patients and have minimal side effects. Agents with >15% response rates in patients relapsing after initial combination chemotherapy include gemcitabine, topotecan, liposomal doxorubicin, and bevicizumab. Bevicizumab is a monoclonal antibody that targets the vascular endothelial growth factor. Initial trials produced a 17% overall response rate in heavily pretreated patients. However, hypertension, thrombosis, and bowel perforations have been reported in some trials. Patients with tumors of low malignant potential, even with advanced-stage disease, have longer survivals (80–90%) when managed with surgery alone. Radiation and chemotherapy do not improve outcome. Ovarian Germ Cell Tumors Fewer than 5% of all ovarian tumors are germ cell in origin. They include teratoma, dysgerminoma, endodermal sinus tumor, and embryonal carcinoma. Germ cell tumors of the ovary generally occur in younger women (75% of ovarian malignancies in women <30), display an unusually aggressive natural history, and are commonly cured with less-extensive nonsterilizing surgery and chemotherapy. Women cured of these malignancies are able to conceive and have normal children. These neoplasms can be divided into three major groups: (1) benign tumors (usually dermoid cysts); (2) malignant tumors that arise from dermoid cysts; and (3) primitive malignant germ cell tumors, including dysgerminoma, yolk sac tumors, immature teratomas, embryonal carcinomas, and choriocarcinoma. Dermoid cysts are teratomatous cysts usually lined by epidermis and skin appendages. They often contain hair, and calcified bone or teeth can sometimes be seen on conventional pelvic x-ray. They are almost always curable by surgical resection. Approximately 1% of these tumors have malignant elements, usually squamous cell carcinoma. . Chapter 093. Gynecologic Malignancies (Part 4) Patients with stage I disease, no residual tumor, and well or moderately. ovarian malignancies in women <30), display an unusually aggressive natural history, and are commonly cured with less-extensive nonsterilizing surgery and chemotherapy. Women cured of these malignancies