Because most tumors are early stage at diagnosis—and even advanced tumors are exquisitely sensitive to chemotherapy—those with malignant ovarian germ cell tumors generally have an excellent prognosis.98,118 Several retrospective studies have demonstrated that with current platinum-based chemotherapy, 5-year survival rates are 95% to 97%, keeping in mind that the majority of patients are stage I at diagnosis.108,119 Even in disseminated cancer, Lai and associates103 noted an 88% 5-year survival rate for stage III-IV disease.
Recurrent disease may be managed with chemotherapy, radiation therapy, surgery, or some combination of therapeutic modalities. If the patient was only under surveillance after surgery, chemotherapy with BEP is indicated. In the setting of persistence or recurrence after chemotherapy with BEP, options include radiation therapy, highdose chemotherapy with etoposide, cisplatin, and bone marrow transplantation, or the POMB-ACE regimen (cisplatin, vincristine, methotrexate, bleomycin, dactino-mycin, cyclophosphamide, and etoposide).92 Recently, a phase II study of paclitaxel and gemcitibine as salvage therapy in the setting of heavily pretreated, recurrent germ cell tumors demonstrated a 31% objective response (12.5% durable complete response).120
The focus of long-term follow-up in addition to surveillance for disease recurrence has been concerned with the late effects of chemotherapy: infertility and risk of secondary malignancy. Many published retrospective reviews have demonstrated a favorable outcome with regard to return of ovarian function (i.e., return of menstruation and ability to conceive) following combination chemotherapy.121-125 In one study, 61.7% of women who were menarchal before cheomotherapy developed amenorrhea while receiving treatment.122 Return of menses after therapy has been estimated to be between 91.5% and 100%.121,122,125
Fertility outcomes after chemotherapy are not as clearly estimated, since it is not always known how many women have actually attempted conception after therapy. One study that collected this information noted that of 38 women who attempted conception, 29 (76%) were successful.123 In addition, a more recent study noted a similar success rate (75%) among women attempting pregnancy.124 The long-term cancer risk of combination chemotherapy seems to be related to the use of alkylating agents such as etoposide and is dose-related. One study of 616 children who received alkylating agents for treatment of germ cell tumors found that the 10-year incidence of treatment-related acute leukemias was 1% for children who received chemotherapy alone and 4.2% for those who received combination chemotherapy and radiation therapy.126 The apparent threshold dose of etoposide is 2000 mg/m2, with patients who received more than this amount having a risk of leukemia approaching that seen in patients with both chemotherapy and radiation.92
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