Chemotherapy Patients with IA, grade 1 tumors have an excellent prognosis, and no adjuvant therapy is required. For patients whose tumors are stage IA, grade 2 or 3, adjuvant chemotherapy should be used (359–361,374,375–378). Chemotherapy is indicated for patients who have ascites, regardless of tumor grade. The standard approach is BEP. The most frequently used combination chemotherapeutic regimen was VAC, but this regimen is no longer used (359,360,391–397).
The GOG is prospectively studying three courses of BEP therapy for patients with completely resected stages I, II, and III ovarian germ cell tumors (359,360,397). Overall, the toxicity is acceptable, and 91 of 93 patients whose nondysgerminomatous tumors were treated are clinically free of disease. The BEP regimen, which is standard of care for testicular cancer, is also the most appropriate chemotherapy regimen for nondysgerminomatous germ cells tumors of the ovary. As these tumors can progress rapidly, treatment should be initiated as soon as possible after surgery, preferably within 7 to 10 days (398).
The switch from VBP to BEP was prompted by the experience in patients with testicular cancer, in which the replacement of vinblastine with etoposide was associated with a better therapeutic index (i.e., equivalent efficacy and lower morbidity), especially less neurologic and gastrointestinal toxicity. The use of bleomycin seems to be important for this group of patients. In a randomized study of three cycles of etoposide plus cisplatin with or without bleomycin (EP versus BEP) in 166 patients with germ cell tumors of the testes, the BEP regimen had a relapse-free survival rate of 84% compared with 69% for the EP regimen (p = 0.03) (372). Cisplatin may be slightly better than carboplatin in the setting of metastatic germ cell tumors. One hundred ninety-two patients with germ cell tumors of the testes were entered into a study of four cycles of etoposide plus cisplatin (EP) versus four cycles of etoposide plus carboplatin (EC). There were three relapses with the EP regimen versus seven with the EC regimen, although the overall survival of the two groups is identical thus far (373). In view of these results, BEP is the preferred treatment regimen for patients with gross residual disease and has replaced the VAC regimen for patients with completely resected disease.
It is unclear whether adjuvant chemotherapy is indicated or required for all patients with resected immature teratomas. Several reports support the successful management of these patients with surgery alone and close surveillance (390,399). In the largest series, an Intergroup study from the Pediatric Oncology Group and the Children’s Cancer Group, 73 children with immature teratoma (44 of ovarian origin) underwent surgery followed by surveillance. With a median follow-up of 35 months, the overall 3-year event-free survival rates for all patients and those with ovarian teratomas were 93% and 100%, respectively. Thirteen of the 44 girls with an immature ovarian teratoma had microscopic foci of yolk sac tumor in the teratoma; one developed recurrent disease and was successfully treated with cisplatin-based chemotherapy. Of note, 82% of the tumors were grade 1 or 2; however, 92% of those with foci of yolk sac tumor were grade 2or3.