Acute changes of alpha-fetoprotein and human chorionic gonadotropin during induction chemotherapy of germ cell tumors

Thirty-seven consecutive patients with germ cell cancers (34 testicular, three extragonadal) and elevated serum levels of alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) were treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum induction chemotherapy. The AFP and/or HCG normalized in 36 patients. The AFP half-life was 7.9 days between Days 1 and 21 postchemotherapy but 6.0 days between Days 21 and 42 (p less than 0.05). The prolonged AFP half-life between Days 1 and 21 was related to a median increase of 57.5% (range, 22 to 219%) in the AFP level. This increase in the marker value occurred between Days 2 and 9 of therapy (median, Day 5). There was also a median increase of 181% (range, 27 to 600%) in the HCG level at a median of 5 days after the start of therapy. The increase in the AFP and HCG levels occurred in 63 and 70% of evaluable patients, respectively, and correlated with the presence of a large volume of metastatic disease (chi 2 = 8.87). Patients with relapsed or refractory disease had prolongation of the AFP half-life between Days 21 and 42 as compared to nonrelapsed patients. AFP and HCG half-life calculations should be used in the management of patients with germ cell cancers.     

Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using and indirect immunoperoxidase technique.

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotropho-blastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.     

125I-labelled human chorionic gonadotrophin (hCG) as an elimination marker in the evaluation of hCG decline during chemotherapy in patients with testicular cancer.

The rate of reduction in the concentration of serum human chorionic gonadotrophin (hCG) following chemotherapy for germ cell tumours may follow a complex pattern, with longer apparent half-life during later stages of chemotherapy, even in patients treated successfully. The commonly used half-life of less than 3 days for hCG to monitor the effect of chemotherapy in patients with germ cell tumours of the testis may represent too simple a model. 125I-labelled hCG was injected intravenously in 27 patients with germ cell tumours and elevated hCG during chemotherapy. The plasma radioactivity and hCG concentrations were followed. During chemotherapy, the plasma disappearance of hCG showed a biphasic pattern, with an initial fast and a later slow component in all patients. Using the steep part of the hCG plasma disappearance curve, five patients who achieved long-term remission had half-lives longer than 3 days (3.6-6.8 days), whereas four out of five patients not achieving long-term remission had half-lives shorter than 3 days. After the third treatment cycle, eight patients who achieved long-term remission had hCG half-lives longer than 3 days (7.4-17.0 days). In these patients, the plasma disappearance of [125I]hCG was equivalent to that of hCG. Thus, the slow decline of hCG represented a slow plasma disappearance rather than a hCG production from vital tumour cells and could, consequently, not be used to select patients for additional or intensified chemotherapy. The concept of a fixed half-life for plasma hCG during treatment of hCG-producing germ cell tumours is inappropriate and should be revised. Difficulties in interpreting a slow decline of hCG may be overcome by comparing the plasma disappearance of total hCG with the plasma disappearance of [125I]hCG.     

Human chorionic gonadotropin and alpha-fetoprotein in testicular germ cell tumors. An immunohistochemical study in comparison with tissue concentrations

The relation between immunohistochemical demonstration and tissue concentration of humanchorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) was examined in 17 testicular germ cell tumors. There was a good correlation between their results; e.g., a tumor with high hCG concentration contained numerous hCG positive cells, and vice versa. The immunoperoxidase localization of hCG and AFP was investigated in 57 tumors including above 17. HCG was revealed in syncytiotrophoblastic giant cells of seminoma or embryonal carcinoma as well as syncytial cells of choriocarcinoma, and on rare occasion in mononuclear cells. AFP was localized in tumor cells of yolk sac tumor or embryonal carcinoma and occasionally hyaline globules. No cell was stained concomitantly with hCG and AFP. Pathogenetical significance of cells positively stained was discussed.     

The value of serial measurement of both human chorionic gonadotropin and alpha-fetoprotein for monitoring germinal cell tumors.

Quantitative serial serum measurements of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) levels using sensitive double-antibody radioimmunoassays were performed in nine patients with germinal cell tumors before and during treatment. The sera of eight of the nine were found to have a hCG marker and five of the nine an AFP marker. The sera of four patients were found to have both. Serial serum levels of hCG, of AFP, or both were useful for monitoring disease activity during therapy in all nine patients. In two patients tumor masses failed to diminish during chemotherapy, but the tumor markers fell appropriately. At surgery one patient had a mature teratoma, the other a mature teratoma with a microscopic focus of an embryonal cell tumor. In one patient tumor reactivation was reflected by the emergence of only one of two previously elevated tumor markers. One patient had a rise in hCG, another a rise in both markers coincident with recurrence of tumor. Serial measurements of AFP and hCG are useful for following the response to therapy of germinal tumors, and can assist in making therapeutic decisions.     

Two-drug therapy in patients with metastatic germ cell tumors.

Eighty-two patients with metastatic germ cell tumors (GCT) treated with two-drug therapy consisting of etoposide and cisplatin were evaluated for late relapse. Good-risk GCT was defined using Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. Etoposide was given at 100 mg/m2 on days 1 to 5 and cisplatin was given at 20 mg/m2 on days 1 to 5; therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000/microliters or a platelet count of less than 100,000/microliters. Drug doses were not attenuated for myelosuppression. Seventy-six of 82 evaluable patients achieved a complete response (CR). Seventy-two patients had a CR to chemotherapy alone. Forty-six (56%) patients had excision of residual abnormalities: 11 had teratoma in the resected specimen, 31 had necrotic debris or fibrosis, and 4 had a CR after chemotherapy plus complete excision of residual viable GCT. Six patients had an incomplete response to chemotherapy; one of these patients had unresectable mature teratoma and remains progression-free. The median etoposide dose (+/- standard deviation [SD]) was 500 mg/m2/course (+/- 35 mg/m2) and the median cisplatin dose (+/- SD) was 100 mg/m2/course (+/- 6 mg/m2). Nine patients experienced a relapse at 6 to 17.5 months; two patients with nonseminomatous GCT were salvaged by chemotherapy and one patient with seminoma was salvaged by chemotherapy and radiation therapy. The three patients who were salvaged by additional therapy are disease-free at 59 to 63 months. Seventy-one patients (87%) remain disease-free with a median follow-up time of 63 months (range, 33 to 92 months). No relapses have occurred beyond 17.5 months. Etoposide and cisplatin therapy at these doses and schedule results in durable CR without late relapse.     

Logarithmic decrease of serum alpha-fetoprotein or human chorionic gonadotropin in response to chemotherapy can distinguish a subgroup with better prognosis among highly malignant intracranial non-germinomatous germ cell tumors

Intracranial non-germinomatous germ cell tumors (NGGCTs) are a heterogeneous group of tumors. Although alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are considered reliable markers for making diagnosis, the relationship between serum concentration of them and prognosis remains unclear. The present study investigated the decrease of serum tumor markers AFP and HCG as prognostic factors for patients with highly malignant NGGCTs. Eight consecutive patients with AFP > 1000 ng/ml or HCG > 2000 mIU/ml at initial treatments after January 2004 were retrospectively reviewed. Serum AFP or HCG concentration and tumor volume were sequentially measured during the therapeutic period. Six patients were treated by neoadjuvant chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by salvage surgery and/or radiation therapy. A 14-year-old boy with choriocarcinoma and a 2-year-old boy with yolk sac tumor underwent radical resection because of acute hydrocephalus and mass effect on the brain stem, followed by chemotherapy and radiation therapy. Five patients showed complete response and survived at follow-up periods of 9, 26, 41, 63, and 75 months, and the other three showed partial response but subsequent recurrence, finally died. Patients with complete response showed logarithmic decrease of serum AFP to the normal range in response to chemotherapy, but the others did not. Logarithmic decrease and normalization of serum AFP and HCG levels during neoadjuvant chemotherapy can distinguish a subgroup with better prognosis within highly malignant NGGCTs. To determine it, sequential measurement of serum tumor marker level was efficient. Outcomes were still dismal for slow responding patients, but this simple method may indicate more aggressive therapy.     

Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

Background

Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors.

Methods

We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP), and lactate dehydrogenase were measured prior to surgery. Vascular density (VD) and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis.

Results

Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016), AFP ≥ 14.7 ng/mL (p = 0.0001), and hCG ≥ 25 mIU/mL (p = 0.0001). In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04). When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization (p < 0.0001). VEGF expression was not associated with VD or hCG serum levels.

Conclusion

This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.     

Serum and urinary levels of beta human chorionic gonadotrophin in patients with transitional cell carcinoma.

Serum and early morning urine specimens were obtained from 62 patients. The levels of beta human chorionic gonadotrophin (BhCG) in both serum and urine were estimated simultaneously in all cases. At the time of estimation 43 patients had transitional cell carcinoma of the bladder, one had transitional cell carcinoma of the renal pelvis and three had carcinoma in situ (two of whom also had overt carcinoma). Raised serum and urinary levels were found in only three patients, all of whom had poorly differentiated or metastatic transitional cell carcinoma of the bladder. This observation is in accordance with previous studies. In one of these patients, who underwent transurethral resection of her bladder tumour, the urinary levels returned to within normal limits post resection. An additional three patients had elevations of serum BhCG. Two of these three patients had poorly differentiated transitional cell carcinoma present at the time of estimation and one had no sign of recurrence. Using immunoperoxidase staining a retrospective study was undertaken to stain all available sections belonging to patients studied to observe whether BhCG was being produced by the respective tumours. Twelve well differentiated, nine moderately well differentiated and seven poorly differentiated specimens were available. In no case was evidence of BhCG production demonstrated in these tumours despite its presence being demonstrable in positive controls. We confirm the production of BhCG associated with bladder tumours, a feature correlated with poorer differentiation. Studies employing larger patient numbers are necessary to clarify the role of this tumor marker in patients with well differentiated bladder tumours.     

The chemotherapy of metastatic gastric adenocarcinomas with hypersecretion of alpha-fetoprotein or beta-human chorionic gonadotrophin: report of two cases.

The chemotherapy of advanced gastric adenocarcinomas (GAs) is based on agents such as cisplatin, 5-fluorouracil and anthracyclins. Reproducible objective response rates are reported as approximately 40%. However, the median survival remains short, not exceeding 10 months. Amongst GA, a subset of tumours with increased plasma alpha-fetoprotein (alphaFP) and/or beta human chorionic gonadotrophin (betaHCG) levels form a well-defined histopathological entity. This subgroup has been associated with poor prognosis, due to the presence of poorly differentiated and rapidly proliferating cells. No specific chemotherapy has been proposed for this particular form of GA. We report two cases of patients with GA and hypersecretion of alphaFP and/or betaHCG. Despite bulky liver metastases and resistance to two standard chemotherapy regimens, both patients exhibited sensitivity to chemotherapy combining bleomycin, oxaliplatin and etoposide. These results suggest that patients with this particular subset of GA may benefit from chemotherapy regimens similar to those given to germ-cell tumour patients.     

Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors.

PURPOSE: Elevated total serum cholesterol levels have been reported recently in a group of patients with metastatic testicular cancer after treatment with cisplatin combination chemotherapy. We have studied the lipid profile of a similar group of patients in an attempt to confirm this observation. PATIENTS AND METHODS: Fasting plasma lipid concentrations were measured in 47 patients with advanced germ cell tumors who were previously treated with a cisplatin combination chemotherapy. The values obtained for mean total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1, and apolipoprotein B concentrations were compared with those obtained from a control group of 59 patients with germ cell tumors who were not treated with chemotherapy and with data from the New Zealand male population. Median time from the completion of chemotherapy to lipid measurement in the treated group was 50 months (range, 2 to 138 months). The median total dose of cisplatin given was 720 mg (range, 300 to 1,625 mg). RESULTS: Mean total plasma cholesterol concentrations in the cisplatin group (5.87 mol/L) and the control group (5.70 mmol/L) did not differ significantly (P > .4). There was no significant difference for any of the variables between the chemotherapy and control groups and those of the New Zealand male population. There was a trend toward higher mean triglyceride concentrations in the chemotherapy group, but this did not reach significance. CONCLUSIONS: We have not demonstrated an elevation in total plasma cholesterol after cisplatin chemotherapy as has been reported by previous investigators. Our results suggest that in these patients, cisplatin-containing combination chemotherapy is not associated with a significant adverse effect on plasma lipid profile.     

False elevations of human chorionic gonadotropin associated to iatrogenic hypogonadism in gonadal germ cell tumors

Radioimmunoassay (RIA) for fraction beta of the chorionic gonadotropin hormone (HCG-beta subunit) has a clinical value in the management of patients with gonadal germ cell tumors (GCT). Treatment of disease causes temporary or permanent iatrogenic hypogonadism and secondary plasmatic elevations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Small but significant cross-reactions with LH have been observed, resulting in spurious elevations of HCG, as result, also in part, of the lack of specificity of the RIA. Twelve patients with complete response showed high HCG follow-up levels between 1.7 and 7.8 mIU/ml; simultaneous determination of LH and FSH resulted, also, in high levels: 79.9 to 24.9 mIU/ml and 80 to 19.2 mIU/ml, respectively, in females, and 78 to 18 mIU/ml and 65.1 to 5 mIU/ml, respectively, in males. Administration of exogenous hormones resulted in all cases in reduction of LH and FSH values and normalization of HCG. Therefore, relationship between spurious elevations of HCG and the iatrogenic hypogonadism is clarified through this simple technique that is of most importance as regards the adoption of the appropriate therapy.     

Salvage high-dose chemotherapy in patients with germ cell tumors: an Italian experience with 84 patients

BACKGROUND: High-dose chemotherapy (HDCT) followed by hematopoietic stem cell support (HSCS) potentially may be curative in patients with germ cell tumor (GCT) who develop recurrent tumors or who have an inadequate response after receiving standard-dose chemotherapy. The authors report their experience with HDCT as salvage therapy for patients with GCT. METHODS: Between 1986 and 2000, 84 patients with GCT, with a median age 29 years (range, 15-50 years), were treated with 105 courses of HDCT with HSCS. Patients were stratified into good, intermediate, and poor risk categories according to a validated prognostic index. RESULTS: Overall, 28 patients (33%) have been continuously disease free. In the good risk group, 24 patients (69%) have been continuously disease free compared with 4 patients (13%) in the intermediate risk group (P < 0.001) and 0 patients in the poor risk group (P < 0.001). Treatment-related mortality occurred only among patients in the poor risk (n = 6 patients) and the intermediate risk groups (n = 4 patients). CONCLUSIONS: In the authors' experience, HDCT induced impressive long-term remissions as salvage treatment among patients in the good risk group. Moreover, the use of validated prognostic classifications may contribute to a better definition of the role of HDCT other than improving the outcome of patients with GCT. The definitive statement on the possible role of HDCT in patients with GCT will derive from the ongoing Phase III randomized studies.     

Incidence of late-relapse germ cell tumor and outcome to salvage chemotherapy.

PURPOSE: To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. PATIENTS AND METHODS: Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. RESULTS: Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. CONCLUSION: Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.     

Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience.

BACKGROUND: Results of second-line chemotherapy in patients with extragonadal non-seminomatous germ cell tumor (NSGCT) appear inferior to results in testicular NSGCT. Patients with retroperitoneal NSGCT achieve a comparable long-term survival rate of 30%, but the salvage rates of patients with mediastinal primary are less than 10%. We conducted a retrospective analysis on patients with mediastinal and retroperitoneal NSGCT treated with second-line high-dose chemotherapy (HDCT) registered with the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS AND METHODS: Between 1987 and 1999, 59 registered patients with retroperitoneal (n=37) and mediastinal (n=22) primary NSGCT, median age 28 years (range 18-60), were treated with second-line HDCT. All had received cisplatin-containing chemotherapy as first-line treatment. RESULTS: Toxic death occurred in three cases (5%). With a median follow-up of 58 months (range 14-114), 18/59 patients (30%) continue to be disease-free. Of three patients who had a disease recurrence after HDCT, one patient achieved a disease-free status with further chemotherapy and surgery. In total, 19 patients (32%) are currently disease-free. Sixteen of 37 patients (43%) with retroperitoneal NSGCT, and three of 22 patients (14%) with mediastinal NSGCT are currently alive and disease-free. CONCLUSIONS: Second-line HDCT might represent a possible option for patients with retroperitoneal primary NSGCT. New salvage strategies are needed for patients with mediastinal NSGCT.     

Hyperthyroidism in men with germ cell tumors and high levels of beta-human chorionic gonadotropin.

A retrospective review was done on all high volume choriocarcinomas and other germ cell tumors of men with serum beta-human chorionic gonadotropin (beta-HCG) levels greater than 50,000 mIU/ml to determine the incidence and characteristics of hyperthyroidism in this setting. Nineteen patients were identified with high beta-HCG levels, but because 2 did not have thyroid function tests performed, the cases of only 17 patients were evaluable. Of these, 14 (82%) had primary testicular carcinoma and 3 (18%) had extragonadal tumors. Beta-HCG levels on presentation ranged from 80,000 to 3,058,000 mIU/ml, with a median of 243,500 mIU/ml. Seven of the 17 evaluable cases (41%) had T4 serum levels higher than 12 micrograms/dl (normal level 4 to 12 micrograms/dl) with a median value of 15.4 micrograms/dl (range, 12.6 to 33.5 micrograms/dl); serum T4 levels correlated with beta-HCG levels (r = 0.84). All seven patients with elevated T4 levels had beta-HCG values greater than 200,000 mIU/ml, and three of these seven had clinical manifestations that could be attributed to an elevated serum T4; only one patient required specific antithyroid treatment; and after control of primary disease, all other patients had normalization of thyroid function. The most common manifestations of hyperthyroidism in our series were tachycardia, hypertension, and a systolic flow murmur; none of the patients had thyroid gland enlargement. We conclude that subclinical hyperthyroidism is a relatively common phenomenon in germ cell tumors of men with high levels of beta-HCG and that control of the primary disease results in serum T4 level normalization.     

Predicting factors for collection of peripheral blood stem cells in patients with advanced germ cell tumors after cisplatin-based combination chemotherapy

The objectives of this study were to identify the predictive factors for the mobilization of CD34 positive peripheral blood stem cells (PBSC) and to determine the optimal timing of PBSC harvest in patients with advanced germ cell tumors after cisplatin-based combination chemotherapy. Thirty-eight patients with advanced germ cell tumors were enrolled in this study. We undertook a retrospective analysis of 124 aphereses performed between March, 1994 and December, 1999. The predictive value for the optimal timing of PBSC harvest was determined by the analysis of the correlation factors between the number of harvested CD34 positive cells and several clinicopathological factors. The mean number of CD34 positive cells obtained at a single apheresis was 5.38 x 10(6)/kg, and the mean cumulative number of CD34 positive cells in each patient was 24.07 x 10(6)/kg. The number of CD34 positive cells were significantly correlated to the number of previously performed chemotherapies before PBSC harvest, leukocyte count and the percentage of immature leukocytes (myelocytes plus metamyelocytes) (p=0.0098, p=0.011, and p<0.0001, respectively). Multivariate analysis revealed that the number of chemotherapies and the percentage of immature leukocytes were independent predictors for the number of harvested CD34 positive cells (p=0.012 and p=0.016, respectively). The present findings suggest that PBSC harvest should be performed during first-line chemotherapy, and that the monitoring of the percentage of immature leukocytes could be a useful predictor for determining the optimal timing of PBSC harvest.     

Intensive induction chemotherapy with CBOP/BEP in patients with poor prognosis germ cell tumors.

PURPOSE: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. PATIENTS AND METHODS: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. RESULTS: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P =.24). CONCLUSION: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.