Advanced Nonseminomatous Germ Cell Tumors Research Articles

Improved clinical outcome in recent years for men with metastatic nonseminomatous germ cell tumors: Carver BS, Serio AM, Bajorin D, Motzer RJ, Stasi J, Bosl GJ, Vickers AJ, Sheinfeld J. Department of Urology, Sidney Kimmel Center for Prostate and Urologic Cancers, New York, NY

The integration of chemotherapy and surgery for metastatic nonseminomatous germ cell tumors (NSGCT) results in survival rates of greater than 80% overall. We evaluated men undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for NSGCT to determine associations between year of treatment and clinical outcome. We evaluated 504 men who underwent PC-RPLND from 1989 to 2002 for NSGCT at our center. Data were obtained from our prospective surgical database, and a multivariable logistic regression model was constructed to evaluate variables associated with 15-month relapse in 392 patients with complete data. From 1989 to 1997, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 4%, 20%, 23%, and 47% of patients, respectively, compared with 18%, 26%, 11%, and 38%, respectively, from 1998 to 2002 (P < 0.001). The median prechemotherapy nodal size for 1989 to 1997 and 1998 to 2002 was 5.0 and 3.5 cm, respectively (P < 0.001). On multivariable analysis, prechemotherapy retroperitoneal nodal size (odds ratio [OR], 1.12; 95% CI, 1.03–1.21; P = 0.005) and presence of visceral metastasis (OR, 2.10; 95% CI, 1.02–4.33; P = 0.04) were significantly associated with 15-month relapse. Men who received a complete RPLND were significantly less likely to experience relapse (OR, 0.22; 95% CI, 0.09–0.50; P < 0.0005). In more recent years, men are presenting with less advanced metastatic NSGCT. This stage migration together with effective therapy has resulted in an improved relapse-free survival.

Improved Clinical Outcome in Recent Years for Men With Metastatic Nonseminomatous Germ Cell Tumors

The integration of chemotherapy and surgery for metastatic nonseminomatous germ cell tumors (NSGCT) results in survival rates of greater than 80% overall. We evaluated men undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for NSGCT to determine associations between year of treatment and clinical outcome. We evaluated 504 men who underwent PC-RPLND from 1989 to 2002 for NSGCT at our center. Data were obtained from our prospective surgical database and a multivariable logistic regression model was constructed to evaluate variables associated with 15-month relapse in 392 patients with complete data. From 1989 to 1997, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 4%, 20%, 23%, and 47% of patients, respectively, compared with 18%, 26%, 11%, and 38%, respectively, from 1998 to 2002 (P < .001). The median prechemotherapy nodal size for 1989 to 1997 and 1998 to 2002 was 5.0 and 3.5 cm, respectively (P < .001). On multivariable analysis, prechemotherapy retroperitoneal nodal size (odds ratio [OR], 1.12; 95% CI, 1.03 to 1.21; P = .005) and presence of visceral metastasis (OR, 2.10; 95% CI, 1.02 to 4.33; P = .04) were significantly associated with 15-month relapse. Men who received a complete RPLND were significantly less likely to experience relapse (OR, 0.22; 95% CI, 0.09 to 0.50; P < .0005). In more recent years, men are presenting with less advanced metastatic NSGCT. This stage migration together with effective therapy has resulted in an improved relapse-free survival.

Can we improve the outcome of patients with advanced non-seminomatous germ cell tumors (NSGCT): 16 years experience of a single institution

5092 Background: We performed an analysis to review the outcome of patients (pts) with advanced NSGCT treated in Russian Cancer Research Center, since the introduction of modern chemotherapy (CT) at 1987. Moreover, we analyzed whether the results had improved over the last 6 years. Methods: 589 CT-naive pts with advanced NSGCT received induction etoposide- and cisplatin-based CT from 1987 to 2003. 534 (91%) pts had primary testicular tumor. Most commonly used CT regimens were EP (36%), BEP (52%), and C-BOP-3BEP (9%). Median follow-up was 60 months (range, 2–210) for the pts who survived. Pts survival was compared in accordance with two treatment periods, ‘before 1997’ and ‘after 1997’. Results: Survival rate differed significantly among the IGCCCG prognostic groups. There was a trend toward improved results over the last 6-year period (see table ). The poor prognostic group attained the most pronounced improvement in both PFS and OS (absolute benefit 14%). This fact could be explained by CT intensification (decrease in the number of reasons for treatment delay or dose-reduction on next cycle of CT) and by increase in the rate of post-CT resections of residual tumors. Conclusions: Despite the absence of major changes in advanced NSGCT treatment during the last two decades, there still exists opportunity to improve the outcome of the pts. [Table: see text] No significant financial relationships to disclose.

Successful Chemotherapy for Advanced Nonseminomatous Germ-Cell Tumor in a Patient Undergoing Chronic Hemodialysis

Successful Chemotherapy for Advanced Nonseminomatous Germ-Cell Tumor in a Patient Undergoing Chronic Hemodialysis

Unusual scapular metastasis as initial manifestation of advanced nonseminomatous germ cell tumor of the mediastinum

Primary malignant germ cell tumors of the mediastinum are relatively rare, occurring predominantly in young male adults, and have a poor prognosis. We present a case of a 27-year-old man who initially experienced a persistent, intractable painful sensation over the right lower scapula despite taking an analgesic agent for 2 months. A scapular x-ray film and a whole-body bone scan showed an expansile osteolytic lesion. Excisional biopsy of the scapula revealed a metastatic carcinoma, suggestive of nonseminomatous germ cell tumor origin. Further examination of the whole abdomen and bilateral testes were negative. Chest computed tomography and magnetic resonance imaging showed a primary tumor mass in the anterior mediastinum. Chemotherapy with cisplatin, bleomycin, and etoposide was administered for six courses. The mediastinal tumor mass was markedly reduced in size and remission without evidence of tracer uptake by [(18)F]fluorodeoxyglucose positron emission tomography examination. Six months after chemotherapy, the patient received advanced surgical intervention to remove the mediastinal tumor, the pathologic features of which were similar to the previous scapular lesion. He was doing well at 1-year follow-up.

869 POSTER Prognostic significance of early predicted time to normalization (TTN) of tumor markers in advanced nonseminomatous germ cell tumors (NSGCT): validation study

Despite a high cure rate in men with testicular cancer, some men in the poor-prognosis group have a less favourable outcome. Poor-prognosis non-seminomatous germ-cell tumours (NSGCT) are defined as those with high tumour markers, non-pulmonary visceral metastases or a mediastinal primary site at presentation. When treated with standard chemotherapy regimens, such as bleomycin, etoposide and cisplatin (BEP), cure rates of less than 50% have been achieved in an international pooled analysis. Some strategies aimed at improving results include the use of multi-agent regimens (e.g. POMB/ACE), intensive-induction chemotherapy (e.g. CBOP/BEP), new chemotherapy drugs, such as ifosfamide, gemcitabine, oxaliplatin, paclitaxel, high-dose chemotherapy, including autotransplantation. To date, no schedule has been proven to be better than standard BEP in randomised trials. We will review the published data relating to first-line and salvage treatment of poor-prognosis NSGCT. To advance the management of this disease, physicians treating poor-prognosis disease are urged to support multi-centre trials, such as the recently launched MRC TE23 study comparing BEP and CBOP/BEP.

Post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumors: The impact of time

4581 Background: The integration of chemotherapy and surgery for metastatic non-seminomatous germ cell tumors (NSGCT) results in an overall survival of > 90%. We evaluated NSGCT patients (pts) undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) to assess for associations between year of treatment and clinical outcome. Methods: We evaluated 509 men who underwent PC-RPLND from 1989–2002 for NSGCT at our center. Pts were retrospectively allocated to 3 cohorts according to year of treatment from 1989 to 1992, 1993 to 1997, and 1998 to 2002. Data were obtained from our prospective surgical database and assessed for stage at diagnosis, IGCCCG risk classification, chemotherapy regimen, PC-RPLND histology, and disease free survival. Statistical analysis was performed using SPSS software; p-values < 0.05 were considered significant. Results: From 1989 to 1992, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 3%, 12%, 25% and 54% of patients respectively, compared to 16%, 23%, 17%, and 37%, respectively from 1998 to 2002 (p < 0.001). The prevalence of good, intermediate, and poor risk disease remained similar over time but the need for salvage chemotherapy declined from 21% (1989–1992) to 9% (1998–2002, p = 0.002). Teratoma in the retroperitoneum increased from 34% (1989–1992) to 49% (1998–2002, p = 0.003), while the prevalence of teratoma in the orchiectomy specimen remained similar. The presence of viable NSGCT at the time of PC-RPLND decreased over time. From 1989–1992, 1993–1997, 1998–2002, 19%, 13%, and 6% of patients had persistent viable disease respectively (p = 0.001). Over time, the 5-year actuarial disease free survival has improved (Table). Conclusion: In more recent years men are presenting with less advanced metastatic NSGCT and a smaller percentage require salvage chemotherapy. This stage migration together with effective chemotherapy and surgery has resulted in an improved disease free survival. No significant financial relationships to disclose.

Clinical outcome of retroperitoneal lymph node dissection after induction chemotherapy for metastatic non-seminomatous germ cell tumors.

Retroperitoneal lymph node dissection (RPLND) following induction chemotherapy has been considered a critical component in the comprehensive management of advanced non-seminomatous germ cell tumors (NSGCT). The objectives of the present study were to review the clinical outcome of patients who underwent RPLND and to evaluate the probability of necrosis alone, based on some readily available clinical data for these patients. Forty-seven consecutive patients with NSGCT were treated with first-line chemotherapy at our institution between January 1993 and September 2002. Twenty-four of these patients, who underwent RPLND with normal values of tumor markers after induction chemotherapy, were included in the study. The cause-specific survival rate was calculated using the Kaplan-Meier method. Various predictive factors for the histology were analyzed using multivariate analysis. The pathological findings at resection were necrosis alone in 62.5% of cases, teratoma in 25.0%, and viable cancer in 12.5%. The cause-specific 3-year survival rate of patients who underwent complete and incomplete resection was 100% and 50.0%, respectively. Among several clinical factors, prechemotherapy tumor size less than 50 mm was found to be an independent predictor of necrosis alone (hazard ratio = 4.45, P= 0.04). Metastatic tumor size before chemotherapy appears to be one of the most important factors for the prediction of necrosis alone in the resected specimens of RPLND. The prognosis of patients might be influenced by the degree to which resection has been completed.

841 Prognostic factors in advanced nonseminomatous germ cell tumors (NSGCT): Importance of primary tumor (PT) histology and numbers of negative prognostic factors (NPF)

841 Prognostic factors in advanced nonseminomatous germ cell tumors (NSGCT): Importance of primary tumor (PT) histology and numbers of negative prognostic factors (NPF)

The role of adjunctive postchemotherapy surgery for nonseminomatous germ-cell tumors: current concepts and controversies.

Adjunctive surgical resection of residual disease after chemotherapy is a critical part of the comprehensive management of patients with advanced nonseminomatous germ-cell tumor (NSGCT). Surgical resection is indicated in the presence of residual radiographic abnormalities and normal serum tumor markers. Necrosis, teratoma, and viable carcinoma can be found at any resected site. After induction chemotherapy, necrosis comprises approximately 50% of histologic findings, teratoma 40%, and viable GCT the remaining 10%. A number of investigators have attempted to predict the presence of necrosis in an effort to obviate surgery. A number of variables predictive of necrosis have been identified and tested prospectively, including: degree of tumor shrinkage, size of pre- and posttreatment mass(es), prechemotherapy markers, and teratomatous components in the orchiectomy specimen. However, the risk for a false-negative prediction remains approximately 20%. The most rigorous approach remains a retroperitoneal lymph node dissection (RPLND). Furthermore, the histologic discordance between different sites ranges from 29% to 46%; thus, all sites of residual disease should be resected. The patient's prognosis is influenced by: (1) completeness of resection, and (2) biology of the tumor (histology of residual mass(es), marker status at the time of RPLND, and prior burden of therapy). Surgical boundaries and completeness of dissection should not be compromised in an attempt to preserve ejaculation.

Germ cell tumors in patients infected by the human immunodeficiency virus.

The objective of this study was to assess the natural history of the two disease courses, patient immune system tolerance, and results of therapy in human immunodeficiency virus (HIV)-infected patients with germ cell tumors (GCT). From 1985 to 1996, 34 HIV-infected men received a diagnosis of GCT. Their charts were analyzed retrospectively. Sixteen patients had seminomas, and 18 had nonseminomatous GCTs (NSGCT); 71% had International Union Against Cancer (UICC), 1997 Stage I-II GCTs. At the time of chemotherapy, 69%, 6%, and 25% of patients with advanced NSGCT were in the International Germ Cell Consensus Classification (IGCCC) good, intermediate, and poor prognostic group, respectively. All except 1 of the 10 patients with advanced seminomas were in the IGCCC good prognostic group. At diagnosis of GCT, 85% of patients were classified as having asymptomatic HIV infection or only persistent generalized lymphadenectomy. The median CD4 cell count was 325/microL (range, 6-1125). Overall, 26 patients were given chemotherapy, but the planned dose intensity was respected in only 15 (57%) patients. Severe toxic effects included febrile neutropenia in 35% of patients. During chemotherapy, zidovudine, prophylactic granulocyte colony-stimulating factor (G-CSF), and a Pneumocystis carinii prophylaxis were given in 19%, 23%, and 35% of cases, respectively. CD4 cell count decreased in 7 (64%) of 11 patients during chemotherapy. Infradiaphragmatic radiotherapy was given in 10 cases and was clinically well tolerated. At a median follow-up of 27 months (range, 3-150), 50% of patients were alive, and only 18% of patients died of GCT. Two patients developed a non-GCT malignancy while in complete remission, namely, Hodgkin disease and an acute leukemia. The prognosis of GCT in HIV-infected patients is mostly dictated by the HIV infection. Patients should be treated according to stage and histologic subtype, although dose reduction of chemotherapy might be necessary in approximately half of the patients. Close surveillance of neutrophil and CD4 cells counts, as well as the use of G-CSF and systematic anti-Pneumocystis carinii prophylaxis are recommended during chemotherapy. The use of highly active antiretroviral therapy during chemotherapy for GCT requires a prospective assessment.

Postchemotherapy Residual Masses in Germ Cell Tumor Patients. Content, Clinical Features, and Prognosis

No AccessJournal of UrologyUrological Survey: Abstracts: Diagnostic Urology and Testis Cancer1 Jun 1999Postchemotherapy Residual Masses in Germ Cell Tumor Patients. Content, Clinical Features, and Prognosis S.P. Stenning, M.C. Parkinson, C. Fisher, G.M. Mead, P.A. Cook, S.D. Fossa, A. Horwich, W.G. Jones, E.S. Newlands, R.T. Oliver, A.E. Stenwig, and P.M. Wilkinson S.P. StenningS.P. Stenning More articles by this author , M.C. ParkinsonM.C. Parkinson More articles by this author , C. FisherC. Fisher More articles by this author , G.M. MeadG.M. Mead More articles by this author , P.A. CookP.A. Cook More articles by this author , S.D. FossaS.D. Fossa More articles by this author , A. HorwichA. Horwich More articles by this author , W.G. JonesW.G. Jones More articles by this author , E.S. NewlandsE.S. Newlands More articles by this author , R.T. OliverR.T. Oliver More articles by this author , A.E. StenwigA.E. Stenwig More articles by this author , and P.M. WilkinsonP.M. Wilkinson More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)68882-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Postchemotherapy Residual Masses in Germ Cell Tumor Patients. Content, Clinical Features, and Prognosis." The Journal of Urology, 161(6), pp. 2024–2025 References 1 : Role of postoperative chemotherapy (CT) in radically resected residual cancer (Ca.) in advanced nonseminomatous germ cell tumors (NSGCT) in the male. J. Urol.1998; 159: 47. abstract 173. Google Scholar For the Medical Research Council Testicular Tumour Working Party; Medical Research Council Cancer Trials Office, Cambridge, University College London Trust, Institute of Urology and Nephrology, Histopathology Department, Royal Marsden Hospital, Charing Cross Hospital and School of Medicine, London, Royal South Hants Hospital, Southampton, Royal Marsden Hospital, Surrey, Cookridge Hospital, Leeds and Christie Hospital, Manchester, United Kingdom, and Norwegian Radium Hospital, Oslo, Norway© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 161Issue 6June 1999Page: 2024-2025 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.MetricsAuthor Information S.P. Stenning More articles by this author M.C. Parkinson More articles by this author C. Fisher More articles by this author G.M. Mead More articles by this author P.A. Cook More articles by this author S.D. Fossa More articles by this author A. Horwich More articles by this author W.G. Jones More articles by this author E.S. Newlands More articles by this author R.T. Oliver More articles by this author A.E. Stenwig More articles by this author P.M. Wilkinson More articles by this author Expand All Advertisement Loading ...

Long-term results of operative therapy for metastasized non-seminomatous germ cell tumours (NSGT) in advanced tumour stages

We present long-term results (minimum follow-up 5 years) in 145 patients with advanced non-seminomatous germ cell tumours, who underwent radical retroperitoneal lymphadenectomy (RPLA) after chemotherapy. We correlated patients' outcomes (death of disease) to different kinds of chemotherapy and to intraoperative findings. We found that patients who were treated by a modified Einhorn scheme with cisplatin, etoposide and bleomycin have a good prognosis. In all, 90% showed no evidence of disease (NED). The NED rate was significantly lower in patients who were treated by sequential alternative chemotherapy (DOD = 37%). We determined the following prognostic factors which predict a poor outcome: salvage RPLA in the case of progressive disease or tumour marker increase during chemotherapy (DOD = 89%, P < 0.0001) residual tumour in multiple-organ systems (DOD = 41%, P = 0.0006) vital tumour in RPLA specimen (DOD = 53%, P < 0.0001) residual tumour mass > 5 cm (DOD = 41%, P = 0.0188). We found that histopathological findings of the primary tumour and tumour stage IIc-IIIc according to the Lugano classification have no prognostic significance for death of disease.

Treatment of men with metastatic non-seminomatous germ cell tumours with cyclical POMB/ACE chemotherapy

An alternating combination chemotherapy schedule for advanced nonseminomatous germ cell tumours (NSGCT) has been in use since 1977. Three hundred thirty-nine men with metastatic NSGCT were treated with POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide), including 42 who had received previous chemotherapy or radiotherapy. Previously untreated patients were classified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model, and 31% were in the worst prognostic group. The median follow-up is eight years. The overall survival at five years is 82% (95% confidence interval (CI); 78%-85%). The survival of untreated patients exceeded that for previously treated patients (log-rank P = 0.04) and of testicular tumours exceeded that for primary extragonadal tumours (log-rank P < 0.0001). The survival of men with IGCCCG poor prognosis disease at three years is 75% (95% CI: 65%-84%) compared to 50% in the large cohort which was used to derive the model. There were five early treatment related deaths. In addition, five patients developed acute leukaemia, one developed a second primary lung adenocarcinoma, one man died of pulmonary fibrosis and three men died of cerebrovascular or cardiovascular disease. The POMB/ACE schedule has been employed in a large series of men with metastatic NSGCT over two decades. The fatal toxicity is equivalent to that described for simpler regimens. It yields equivalent response rates and survival in men with good prognosis disease and appears to achieve better survival in patients with poor prognosis disease.

Surgical resection in patients withnonseminomatous germ cell tumor who fail to normalize serum tumor markers after chemotherapy

Objective Patients with high-stage nonseminomatous germ cell tumors treated with platinum-based chemotherapy who have residual radiographic evidence of disease and fail to normalize tumor markers present a difficult clinical dilemma. Some authors feel that these patients are not appropriate surgical candidates. Our practice has been to offer certain patients salvage surgery in an attempt for cure. This report is designed to review that experience and critically analyze the results. Method We report a series of 16 such patients with advanced-stage nonseminomatous germ cell tumors who had persistently elevated alpha fetoprotein and/or human chorionic gonadotropin. All underwent resection of all radiographically evident sites of residual disease following induction or salvage chemotherapy. Results Ten patients had only retroperitoneal (RP) metastasis. Six patients had morethan one site of residual disease—4 RP and lung, 2 RP and liver. There were no postoperative deaths. The mean postoperative stay was eleven days (range 7 to 36 days). Six patients (37%) are alive and free of disease at a mean of seventy-four months following surgery (range 20 to 145 months). Five had RP disease only. Ten patients died of disease at a mean of eight months postoperatively (range 5 to 21 months). Conclusions Patients with advanced nonseminomatous germ cell tumor who fail tonormalize their serum tumor markers after adequate platinum-based chemotherapy should be considered for surgical resection of all radiographically evident residual disease. In select cases this practice offers the only viable chance for cure.

Distribution of Retroperitoneal Metastases After Chemotherapy in Patients With Nonseminomatous Germ Cell Tumors

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.

Excision of residual masses after platinum based chemotherapy for non-seminomatous germ cell tumours

Between January 1980 and June 1987, 42 patients receiving platinum based combination chemotherapy for advanced non-seminomatous germ cell tumours had residual masses, detected by computed tomography, after four or six treatment courses without tumour marker evidence of active disease. Resection of retroperitoneal (n = 32), pulmonary (n = 4) or thoracoabdominal (n = 2) disease revealed residual malignancy in nine patients (21%), differentiated teratoma in 14 (33%) and fibrosis or necrosis in 15 (36%). Laparotomy showed no evidence of a mass in four instances.Of the 42 patients, 14 had malignant teratoma undifferentiated in the primary tumour only one of whom (7%) had evidence of malignancy in the specimen resected post-chemotherapy. Conversely, six of 15 patients (40%) whose primary tumour was malignant teratoma intermediate had residual malignant tissue after treatment.With a median follow up of 36 months from post-chemotherapy surgery, 36 patients (86%) are continuously disease-free. Relapses occurred in one of nine patients with residual malignancy (11%), three of 14 with differentiated teratoma (21%), one of 15 with necrosis or fibrosis (7%) and in one patient who had a normal laparotomy. Four patients have died from their tumours, but two are currently disease-free following further surgery and chemotherapy for relapse.Neither primary nor post-chemotherapy histology was predictive of relapse, and although relapse was numerically more common in patients whose residual mass was incompletely excised (three of 12), this was not statistically significant.

Significance of Salvage Lymphadenectomy in the Therapeutical Concept of Advanced Nonseminomatous Germ Cell Tumors

A retrospective study reports 65 patients with metastatic disease from nonseminomatous germ cell testicular tumors who underwent a salvage lymphadenectomy either to remove a residual mass or to confirm a complete clinical response after polychemotherapy. Scarring was found in 23 patients (35%), differentiated teratoma in 25 patients (39%) and residual cancer in 17 patients (26%). Of the 12 patients staged as complete responders 2 were found to have cancer, 4 teratoma and 6 fibrosis. Neither tumor markers nor CT scan could accurately predict which patients with residual masses would have cancer, mature teratoma or necrosis. Thus needle biopsy or limited resection is inadequate in its ability to detect persistent vital tumor. After a follow-up of 10-106 months 49 patients (75%) are living with no evidence of disease. 12 patients (19%) died of tumor progress. The most critical prognostic determinant was the nature of the tissue resected. 21 (91%) of 23 patients with only fibrous or necrotic elements are living with no evidence of disease. However, of 17 patients with persistent cancer in the resected tissue only 8 patients (47%) fared well. Our experience confirms the original concept which called for postchemotherapeutic tumor surgery in all patients who demonstrated either a partial or complete clinical response.

Chemotherapy with maximally tolerable doses of VP 16-213 and cyclophosphamide followed by autologous bone marrow transplantation for the treatment of relapsed or refractory germ cell tumors

Eleven patients with advanced nonseminomatous germ cell tumors (NSGCT), who relapsed after or were refractory to standard dose cisplatin-based remission induction chemotherapy, were treated in a phase II clinical trial with VP 16-213 2500 mg/m 2 and cyclophosphamide 7 g/m 2 . Both drugs were given in maximally tolerable doses regarding extramedullary toxicity. Urothelial damage due to cyclophosphamide was prevented by the administration of mesnum. Autologous bone marrow was infused on day 7 to prevent long lasting medullary toxicity. Because of the disappointing results in the first three patients, a second treatment step was added. The next eight patients were treated with 2500 mg/m 2 VP 16-213 divided and given on days 1–2–3 and after full bone marrow recovery with total doses of VP 16-213 2000 mg/m 2 plus cyclophosphamide 7 g/m 2 divided and given on days 29–30–31, followed by autologous bone marrow transplantation (ABMT) on day 35. Toxicity to high-dose VP 16-213 plus cyclophosphamide followed by ABMT consisted of mucositis, nausea, vomiting and diarrhea. No cardiac toxicity or hemorrhagic cystitis occurred. The mean duration of leukopenia and thrombopenia was 14 and 13 days respectively. The additional, preceding treatment with VP 16-213 as a single agent caused mucositis, and leukopenia and thrombopenia for a mean number of 9 and 6 days respectively. Seven responses were obtained: two complete responses of 46 and 66+ weeks respectively and five partial responses with a median response duration of 12 weeks. The median survival time was 40 weeks. This regimen of one or two courses with maximally tolerable doses of VP 16-213 plus cyclophosphamide and ABMT is not sufficient to salvage a substantial number of patients with relapsing or refractory NSGCT.

High-dose cis-platinum combination chemotherapy in advanced nonseminomatous malignant germ cell tumours with emphasis on nephrotoxicity

High-dose cis-platinum treatment (180 mg/m2 per cycle) in combination with VP16 and bleomycin was given to 14 patients with highly advanced nonseminomatous malignant germ cell tumours (total: 31 cycles). Cis-platinum was administered in infusions of 0.9% NaCl given daily for 3 days with 3-week intervals. An intensive hydration regimen (71 NaCl/day) provided a urinary output of at least 1000 ml/4 h. The response and side effects were evaluated. Ultimately 11 of 12 patients evaluable for treatment effect were rendered tumour-free and are alive with NED. All 14 patients were evaluable for toxicity; 2 developed life-threatening lung edema during the initial prehydration period and did not continue the high-dose cis-platinum schedule. After one to four cycles of high-dose cis-platinum treatment the 131I-Hippuran clearance was reduced by 28%. Decreased kidney function evaluated by 131I-Hippuran clearance was the reason for discontinuation of treatment in 5 patients. Patients with ureteric obstruction represented a high-risk group for reduction of kidney function. High-dose cis-platinum therapy is an intensive treatment demanding a high level of investment of resources, which has promising response rates in patients with highly advanced malignant germ cell tumours. Short-term clinically significant reduction of the kidney function can be avoided by intensive hydration of the patient.