Treatment of ovarian germ cell tumors with a 3-day bleomycin, etoposide, and cisplatin regimen: a prospective multicenter study. PVB chemotherapy in patients with recurrent or advanced dysgerminoma: a Phase II study of the EORTC Gynaecological Cancer Cooperative Group. Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group. Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891. A phase II study of high-dose cisplatin, vinblastine, bleomycin, and etoposide (PVeBV regimen) in malignant nondysgerminomatous germ-cell tumors of the ovary. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.
BACKGROUND Ovarian germ cell tumors ( OGCT ) are highly curable when treated with cytoreductive surgery and platinum-based chemotherapy . We evaluated the safety and activity of a 3-day modified bleomycin , etoposide , and cisplatinum ( mBEP ) regimen in patients with OGCT . PATIENTS AND METHODS Patients with FIGO stages I-IV OGCT were treated with three ( stages I-III complete resection ) or four cycles ( incomplete resection or stage IV ) of bleomycin 15 mg iv , etoposide 120 mg/m(2 ) iv , and cisplatin 40 mg/m(2 ) iv for 3 days every 3 weeks . RESULTS Forty-eight patients ( 14 with dysgerminoma and 34 with non-dysgerminomatous tumors ) were included in our study . Most patients had stage I disease ( 65 % ) and complete resection of their tumor ( 67 % ) . Twenty percent of patients developed grade 3 or 4 neutropenia with 4 episodes of neutropenic fever . During follow-up ( median : 5 years ) , two patients developed progressive disease including one patient who died . All patients with stage I or II disease and all patients with dysgerminoma remain free of disease . However , 20 % of patients with non-dysgerminomatous tumors stage III or IV experienced progressive disease . CONCLUSION The modified 3-day BEP regimen was safe and effective in patients with OGCT . Further improvements are needed for patients with advanced , suboptimally debulked non-dysgerminomatous tumors Dysgerminoma accounts for 1 % of all ovarian cancers and for 50 % of all ovarian germ cell malignancies . Low stage patients ( 50 % ) can be cured with local treatment . The aim of this trial was to study the objective tumour response rate and toxicity of PVB ( cisplatin , vinblastine , bleomycin ) chemotherapy in patients with pure advanced or recurrent dysgerminoma . Eighteen eligible patients with advanced dysgerminoma were entered into this study . Three patients had local bulky recurrence only ; all the others also had metastatic disease . The median age at entry was 27 years ( range 1348 ) . Seventeen patients had had prior surgery and one had undergone prior radiotherapy .  The WHO performance status was 0 in 12 patients , 1 in three patients , and 2 in three patients . The treatment consisted of : intravenous or intramuscular bleomycin 30 mg on days 2 , 9 and 16 , intravenous vinblastine 0.15 mg/kg on days 1 and 2 , and intravenous cisplatin 20 mg/m2 on days 1 - 5 . This regimen was given at 3-week intervals for a total of four cycles . Twelve patients obtained a complete response ( 66 % ) , five a partial response ( 28 % ) , and one could not be evaluated because radiotherapy was administered immediately after chemotherapy . After a median follow-up of 76 months ( range 4 - 132 ) , 14 ( 78 % ) patients were alive and well . Two died of disease progression , one of neutropenic septicaemia and one of lung fibrosis . No unusual toxicity was reported . Alopecia , as well as nausea and vomiting , were common . Leucopenia ( 78 % ) , thrombocytopenia ( 17 % ) and infection ( 11 % ) were the other severe ( grade 3 - 4 ) side effects . The PVB chemotherapy regimen is highly effective in patients with advanced ovarian dysgerminoma . However , the BEP ( bleomycin , etoposide , cisplatin ) regimen , which is equally as potent and less toxic , is preferred OBJECTIVE This study was design ed to evaluate the effect of adjuvant chemotherapy with carboplatin and etoposide in patients with completely resected stage IB-III dysgerminoma . METHODS Eligible patients were treated with three courses of carboplatin 400 mg/m(2 ) on day 1 plus etoposide 120 mg/m(2 ) on days 1 , 2 , and 3 every 4 weeks for three courses . RESULTS Forty-two patients were entered on this trial , of whom 39 were eligible . No patient suffered a recurrence of dysgerminoma , but one patient ultimately died of lung adenocarcinoma . One patient was excluded on pathology review ( elements of endodermal sinus tumor were present ) developed recurrent tumor and died despite further therapy . As expected , the regimen was well tolerated . Median follow-up of surviving patients is 7.8 years ( range : 2.86 months to 10.92 years ) . CONCLUSION The regimen used in this study is an alternative to cisplatin , etoposide , and bleomycin ( BEP ) for selected patients for whom minimizing toxicity ( particularly neuropathy ) is critical or for whom reduction in the number of treatment days is important PURPOSE To determine whether children with localized gonadal malignant germ cell tumors ( MGCT ) stage II testicular and stages I and II ovarian treated with four cycles of st and ard-dose cisplatin combined with etoposide and low-dose bleomycin ( PEB ) have an event-free survival ( EFS ) of at least 85 % without significant toxicity . PATIENTS AND METHODS Between May 1990 and July 1995 , eligible pediatric patients with stage II or recurrent from stage I ( as a stage II ) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Children 's Cancer Group study .  PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1 , cisplatin 20 mg/m2/d on days 1 to 5 , and etoposide 100 mg/m2/d on days 1 to 5 . Patients received four cycles of therapy at 21-day intervals . RESULTS Seventy-four patients with a median age of 10.5 years ( range , 8.7 months to 16.7 years ) were enrolled . Primary sites included : stage II testicular ( n = 17 ) , stage I ovarian ( n = 41 ) , and stage II ovarian MGCT ( n = 16 ) . Treatment with st and ard PEB result ed in 6-year EFS of 95 % and overall survival ( OS ) of 95.7 % . EFS and OS by primary site were as follows : stage II testicular , 100 % and 100 % ; stage I ovarian , 95.1 % and 95.1 % ; and stage II ovarian , 87.5 % and 93.8 % , respectively . Two patients died from recurrent disease , and one patient died of secondary acute myelocytic leukemia . Infrequent grade 3 to 4 hematologic toxicity was reported . No grade 3 to 4 renal , pulmonary , or ototoxicity was observed . CONCLUSION Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT Fourteen patients with malignant nondysgerminomatous germ-cell tumors of the ovary were treated with a combination of high-dose cisplatin , vinblastine , bleomycin , and etoposide ( PVeBV regimen ) . Nine patients received PVeBV as primary postoperative therapy , of whom four had no residual disease . Four patients received PVeBV for recurrent disease . One patient underwent PVeBV therapy as second-line treatment . Three patients with initial poor prognostic features were treated with early high-dose chemotherapy with autologous bone marrow rescue as consolidation therapy after two cycles of PVeBV . Ten of 14 patients ( 71 % ) are progression-free with a median follow-up of 6 year . Equal efficacy and less toxicity favor the combination of bleomycin , etoposide , and cisplatin ( BEP ) as st and ard treatment of ovarian germ-cell tumors in the 1990s PURPOSE This multicenter , r and omized phase III clinical trial evaluated the efficacy of etoposide plus carboplatin ( EC ) versus etoposide plus cisplatin ( EP ) in good-risk germ cell tumor ( GCT ) patients . PATIENTS AND METHODS Between October 1986 and December 1990 , 270 patients with good-risk GCTs were r and omized to receive four cycles of either EP or EC . The etoposide dose in all patients was 100 mg/m2 on days 1 through 5 . EP patients received cisplatin at 20 mg/m2 on days 1 through 5 and therapy was recycled at 21-day intervals . For EC patients , the carboplatin dose was 500 mg/m2 on day 1 of each cycle and the EC recycling interval was 28 days . RESULTS Two hundred sixty-five patients were assessable : 131 patients treated with EC and 134 treated with EP .  One hundred fifteen of 131 assessable patients ( 88 % ) treated with EC achieved a complete response ( CR ) versus 121 of 134 patients ( 90 % ) treated with EP ( P = .32 ) . Sixteen patients ( 12 % ) treated with EC relapsed from CR versus four patients ( 3 % ) treated with EP . Therefore , 32 patients ( 24 % ) who received carboplatin experienced an event ( incomplete response [ IR ] or relapse ) compared with 17 of 134 patients ( 13 % ) who received cisplatin ( P = .02 ) . At a median follow-up of 22.4 months , event-free and relapse-free survival were inferior for patients treated with EC ( P = .02 and P = .005 , respectively ) . No difference in overall survival was evident ( P = .52 ) . CONCLUSION Two-drug therapy with EC using this dose and schedule was inferior to therapy with EP . Cisplatin remains as the st and ard platinum analog in the treatment of patients with good-risk GCTs .  Carboplatin should be restricted to investigational trials in GCT PURPOSE This study was performed to determine the effectiveness of postoperative adjuvant chemotherapy in patients with surgically resected ovarian germ cell tumors . PATIENTS AND METHODS After tumor removal and thorough surgical staging , patients were enrolled on this study and treated with three courses of cisplatin , etoposide , and bleomycin ( BEP ) . Re assessment laparotomy was required of consenting , appropriate patients initially , but became an optional procedure in 1989 . RESULTS Of 93 patients assessable on this trial , 89 are continuously free of germ cell cancer . At second-look laparotomy , two other patients were found to have small foci of immature teratoma ; both remain clinical ly free of recurrence . One received subsequent alternate chemotherapy and one did not . Thus , 91 of 93 patients are currently free of germ cell cancer . Follow-up duration ranges from 4.0 to 90.3 months , with 67 patients monitored for longer than 2 years . Acute toxicity was moderate . One patient developed acute myelomonocytic leukemia 22 months after diagnosis . Another patient was noted to have a malignant lymphoma 69 months after protocol treatment . CONCLUSION Three courses of BEP will nearly always prevent recurrence in well-staged patients with completely resected ovarian germ cell tumors and should be given to all such patients . The development of acute leukemia as a complication of treatment is disturbing and m and ates careful long-term follow-up , but is unusual and does not alter the risk-to-benefit ratio of treatment
OBJECTIVE Ovarian germ cell tumors ( OGCTs ) are rare tumors that comprise a diverse group of histologic subtypes that can either be benign or malignant .
Malignant ovarian germ cell tumors ( OGCTs ) historically carried a poor prognosis , especially among those diagnosed with advanced disease .
With the advent of combination chemotherapy , risk of relapse has markedly decreased .
There is limited prospect i ve data on the efficacy of specific chemotherapy regimens in the treatment of malignant OGCTs .
This article critically review s the literature pertinent to the treatment of OGCTs with chemotherapy .