High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.     

Secondary leukemia following ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors in a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of secondary leukemia occurring in a 31-year-old man who received ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) for a refractory testicular cancer (pathology; Seminoma, Embryonal carcinoma, Yolk sac tumor, Choriocarcinoma) with IIIB2 under Japanese classification, poor-risk group under Indiana classification. The initial levels of serum LDH, AFP and beta-HCG were high at 959 IU/l, 1,452 ng/ml and 800 ng/ml. He received total 11 cycles of systemic chemotherapy (2 cycles of PVB regimen, 4 cycles of PEB regimen, 3 cycles of VIP regimen and 2 cycles of ultra high-dose chemotherapy with PBSCT for pulmonary and para-aortic lymph node metastasis following his initial orchiectomy. The total amount of etoposide (VP-16), cisplatin (CDDP), carboplatin (CBDCA) and ifosfamide (IFM), this patient received was 7,225 mg/m2, 1,510 mg/m2 1,750 mg/m2, and 50.5 g. He has survived with CR of disease. Severe and persistent pancytopenia developed 25 months after his initial orchiectomy. Bone marrow examination showed AML (M2 with eosinophilia) under French-America-British (FAB) classification. Therefore, he was diagnosed as secondary leukemia following high-dose chemotherapy. He received total 6 cycles of systematic chemotherapy for the secondary leukemia in the internal department. He is planing to have bone marrow transplantation. To our knowledge, this is the first reported case in the literature relevant to secondary leukemia following ultra high-dose chemotherapy with PBSCT in testicular tumor in Japan.     

Kinetics of peripheral blood CD34-positive cells and the optimum timing for harvesting peripheral blood stem cells during BEP chemotherapy in patients with testicular germ cell tumor

PURPOSE: Recently, high-dose chemotherapy with peripheral blood stem cell (PBSC) rescue has been developed for poor risk testicular germ cell cancer. In this study, we investigated the optimum timing for harvesting PBSCs with the use of bleomycin + etoposide + cisplatin (BEP) chemotherapy, which is a well known first-line regimen for the testicular cancer. MATERIAL AND METHOD: Peripheral blood CD34-positive cell ratios were measured during a total of 10 courses of BEP chemotherapy in 6 patients with metastatic germ cell cancer between 1996 and 1998. We performed 4 apheresis in 3 patients during this period. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) was administrated from the day on which the neutrophil count decreased less than 1,000/microliter. RESULTS: The peripheral blood CD34-positive cell ratios became maximum (3.0-24.6%; average 10.0%) on the day 18 to 21 (median day 19) of BEP chemotherapy with rhG-CSF administration. The maximum ratios of peripheral blood CD34 positive cells were achieved when the number of leukocyte were 6,880-23,600/microliter and exceeded 6,000/microliter after the 18th day of BEP chemotherapy. The average number of collected CD34 positive cells was 9.5 x 10(6)/kg at a single apheresis, and 12.6 x 10(6)/kg per patient. CONCLUSION: Efficient hematopoietic progenitor cells were mobilized by BEP chemotherapy with rhG-CSF administration of first-line setting. Our results suggest that the optimum timing of PBSCs harvest is the day when the numbers of leukocyte exceed 6,000/microliter after the 18th day of BEP chemotherapy and the following day.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

One cycle of bleomycin, etoposide and cisplatin plus two cycles of etopeside and cisplatin chemotherapy in selected patients with low-volume stage II nonseminomatous germ cell tumor of the testis

OBJECTIVE: To assess the feasibility of bleomycin omission from second and third cycles of bleomycin, etoposide and cisplatin (BEP) chemotherapy in low-volume stage II nonseminomatous germ cell tumor patients who achieve a normal tumor marker level after the first cycle of treatment. MATERIALS AND METHODS: Out of 59 nonseminomatous testicular cancer patients with low-volume retroperitoneal disease, serum markers normalized after the first cycle of treatment in 30 cases. 12 patients completed 3BEP (group 1; years 1994-1998) and other 18 patients received etoposide and cisplatin (EP) as second and third cycles of chemotherapy (group 2; years 1998-2004). RESULTS: All patients from each group achieved complete response with chemotherapy alone or by subsequent resection of teratoma or necrosis. There was no relapse with active cancer after the treatment. All patients remained disease-free during the median follow-up period of 97 and 48 months for groups 1 and 2 respectively. CONCLUSIONS: One cycle of BEP plus two cycles of EP chemotherapy was as effective as three standard cycles of BEP. The regimen can be suggested as a less toxic therapeutic alternative in these selected patients. More cases, however, in a prospective randomized setting are required to further verify these data.     

High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

Clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation for patients with advanced germ cell tumor

We examined the clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) in 14 patients with poor-risk advanced germ cell tumors. The mean number of nadir white blood cells was 205 +/- 126/microliter; the mean period of number of white blood cells fewer than 1,000/microliter was at 8-10 days (mean +/- SD; 9.2 +/- 0.92). The nadir number of blood platelet cells was 1.7 +/- 0.70 x 10(4)/microliter; the mean period of number of platelet cells fewer than 5 x 10(4)/microliter was at 12.6 +/- 2.17 days. Of 10 patients treated with super high-dose chemotherapy with PBSCT as induction therapy, 8 patients (80%) showed that the serum tumor marker returned within the normal range after super high-dose chemotherapy. Of 8 patients, 7 underwent resection of the residual tumor. Surgical or pathological CR was obtained in 5 of these 7 patients, 4 patients of whom were alive with no evidence of disease 29 to 49 months after initial consultation: the other patient died with recurrence 20 months after initial visit. On the other hand, super high-dose chemotherapy with PBSCT was performed for one patient as consolidation, and for 3 patients with recurrence. Of these 4 patients, one died from disease 6 months after detection of recurrence. The other 3 patients were alive with no evidence of disease at 7-37 months after initial visit. The 1- and 3-year disease-free survival rates were 88% and 72%, respectively. In conclusion, super high-dose chemotherapy with PBSCT can be done safely and could be useful for patients with poor-risk germ cell tumor.     

Chemotherapy for good-risk germ cell tumors: current concepts and controversies

Through a series of well-designed randomized clinical trials, the treatment of patients with cisplatin-based chemotherapy has evolved such that approximately 90% of patients who have good-risk metastatic germ cell tumor (GCT) will be cured of their disease. At present, first-line chemotherapy for patients who have good-risk metastatic GCT is three cycles of bleomycin/etoposide/cisplatin. An alternative to this is four cycles of etoposide/cisplatin. This article examines the progress that has been made in the development of chemotherapy for good-risk metastatic GCT and raises questions for further consideration and investigation.     

Treatment of advanced testicular cancer and toxicity of chemotherapy

To assess the efficacy and toxicity of chemotherapy for advanced germ cell tumors, 115 patients with testicular and extragonadal germ cell tumors were reviewed. Five-year survival rates of 19 seminoma patients and 96 non-seminoma patients were 84% and 68%, respectively. According to the analysis using three sets of prognostic criteria, Indiana University Classification, International Germ Cell Consensus Classification and K Classification, the 5-year survival rate of poor-prognosis patients was 42-45%. BEP regimen (bleomycin, etoposide and cisplatin) salvaged with VIP (etoposide, ifosfamide and cisplatin) would be the standard therapy for advanced germ cell tumors since high-dose chemotherapy had no advantage on survival over the standard-dose regimen. Early serious toxicities were observed in 18 patients (15.7%), including pulmonary fibrosis, respiratory distress, and sepsis. Poor performance status and prior radiotherapy were risk factors for fatal adverse effects. In terms of late toxicites, out of 76 patients in complete remission for at least one year after cessation of chemotherapy, 31 had numbness of extremities and 29 had tinnitus. Serial semen analyses of 38 patients showed continuous azoospermia or severe oligozoospermia in 22. These data indicated that less toxic therapy was required for good-risk patients to improve the quality of life, while more intensive therapy for poor-risk patients to be cured. Several prognostic criteria should be utilized to properly distinguish good- from poor-risk patients, and decide how to treat each patient.     

High-dose chemotherapy for male germ cell tumor

Today, 20-30% of male patients with advanced germ cell tumor (GCT) do not have durable, complete remission in spite of cis-platinum (CDDP)-based chemotherapy. High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients. Initially HDCT was performed with autologous bone marrow transplantation in heavily treated patients. However, the clinical outcome was not good and the treatment-related death rate was not ignorable. Therefore, earlier introduction of HDCT with peripheral blood stem cell transplantation was preferable as it renders HDCT more effective and less toxic, and multicycle HDCT is feasible. The durable free rate of recent HDCT for refractory GCT patients is 32-65%. HDCT is also performed as first line chemotherapy for poor prognosis GCT patients. Induction chemotherapy followed by multicycles of HDCT was tried. The durable free rate of recent HDCT as first line chemotherapy is 43-73%. Although previous reports suggest the superiority of HDCT, one recent randomized controlled trial (RCT) failed to show an improvement with one cycle of HDCT followed by three cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT. Ongoing RCT comparing multicycles of HDCT with SDCT for poor prognostic GCT patients will clarify the role of HDCT. Recently, new regimens of HDCT containing paclitaxel have been devised. In this review, the history, current status and future of HDCT for advanced or refractory GCT will be discussed.     

Methotrexate,paclitaxel, ifosfamide,and cisplatin in poor-risk nonseminomatous germ cell tumors

ObjectiveThe efficacy and tolerability of M-TIP was evaluated as first-line treatment for patients with poor-risk germ cell tumors (GCT), according to International Germ Cell Cancer Collaborative Group (IGCCCG) criteria.Patients and methodsThirty patients with poor-risk GCT were treated with M-TIP (methotrexate 250 mg/m² given as a 4-hour infusion with folinic acid rescue on day 1, paclitaxel 175 mg/m² given as a 3-hour infusion on day 1, followed by ifosfamide 1.2 g/m² given as a 2-hour infusion and cisplatin 20 mg/m² given as a 2-hour infusion on days 2 to 6) regimen for four cycles.ResultsFive (16.6%, 95% confidence interval [CI]: 2%–31%) patients achieved clinical complete response (cCR) with chemotherapy only, 15 (50%, 95% CI: 31–69%) patients pathologic complete response (pCR) (11 had necrosis/fibrosis and 4 had mature teratoma) and 3 (10%) patients surgical complete response (sCR) for an overall favorable response of 76.6%. Twenty-one patients are continuously disease-free at a median follow-up of 5.3 years (range 0.9–8.4+ years), resulting in a 5-year progression-free survival (PFS) rate of 66.6% (95% CI = 49%–85%) and a 5-year survival rate of 70% (95% CI = 53%–87%). Toxicity was generally mild except for myelotoxicity. Patients with febrile neutropenia were successfully treated with broad spectrum antibiotics and G-CSF support. Hematologic toxicity in this trial was ameliorated with the use of G-CSF. Neurotoxicity and nephrotoxicity were not a problem, since only 6.6% and 3.3% of patients developed sensory neuropathy and renal toxicity, respectively.ConclusionM-TIP is a highly effective (high proportion of patients achieved long-term disease-free status, lack of relapses) and well tolerated regimen for first-line treatment of poor-risk GCT patients. These results have to be compared with the standard BEP chemotherapy or more intensive regimens in multicentre randomized trials.     

Clinical study of high-dose chemotherapy with peripheral blood stem cell transplantation for poor-risk germ cell tumor

Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.     

BEP (bleomycin, etoposide, cisplatinum) chemotherapy as an induction therapy of advanced extragonadal germ cell tumor]

Five patients with advanced extragonadal germ cell tumor (EGGCT) were treated with cisplatinum + vinblastine + bleomycin (BVP) or cisplatinum + etoposide + bleomycin (BEP) chemotherapy as an induction therapy. All patients had high levels of tumor markers and multiple distant metastasis in poor nutritious conditions. Two patients given BVP therapy died 6 and 9 months after the chemotherapy. By contrast, three patients given BEP therapy achieved complete remission and were surviving longer than one year without any evidences of disease. Granulocytopenic fever was seen soon after the first course of BEP therapy. Prophylactic granulocyte-colony stimulating factor (G-CSF) treatment, enabled two of them to receive full dose chemotherapy without any fever attacks. In conclusion, BEP chemotherapy is effective to EGGCT as well as far advanced testicular tumors and G-CSF treatment is useful for achievement of induction chemotherapy to advanced germ cell tumors.     

Prognostic analysis of Japanese men with metastatic germ cell tumors showing favorable response to bleomycin, etoposide and cisplatin as first-line chemotherapy

The objective of this study was to evaluate the efficacy of first-line bleomycin, etoposide and cisplatin (BEP) chemotherapy in Japanese patients with metastatic germ cell tumors (GCTs). Between 1996 and 2006, 88 male patients with metastatic GCTs were treated with first-line BEP at our institution. Of these 88, 47 (16, seminoma; 31, nonseminoma), who did not receive high-dose chemotherapy following BEP because of the normalization of serum tumor markers, were included in this study. The primary site was the testis in 42 patients, retroperitoneum in 3, and mediastinum in 2. The full-dose regimen used for BEP consisted of cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 1 to 5, and bleomycin on days 2, 9 and 16. Therapeutic outcome was assessed according to several clinicopathological parameters. Following 2 to 4 cycles of BEP (median, 4 cycles), alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were normalized in all 47 patients. Eighteen patients (38.3%) achieved a complete response (CR) after BEP alone, while BEP resulted in a partial response and stable disease in the remaining 23 (48.9%) and 6 (12.8%), respectively. In addition, surgical resection of the residual tumors following BEP was performed in 15 patients, of whom 12 (80.0%) and 3 (20.0%) achieved pathological and surgical CR, respectively. At a median follow-up of 27 months, all patients were alive; however, disease recurrence occurred in 5 (seminoma, 1; nonseminoma, 4), and all these 5 were subsequently treated with high-dose chemotherapy as salvage therapy. In this series, 1-, 3- and 5-year recurrence-free survival rates were 95.0, 91.4 and 79.2%, respectively, and, there was no significant difference in recurrence-free survival between patients with seminoma and those with nonseminoma. These findings suggested that patients with metastatic GCTs, regardless of histological subtype (i.e., seminoma or nonseminoma), who showed favorable response to first-line BEP chemotherapy, could achieve an excellent prognostic outcome.     

Clinical study for management of supportive treatment for high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) for intractable testicular tumor

The side effects of high-dose anti-cancer drug chemotherapy with peripheral blood stem cell transplantation (PBCST) for the treatment of intractable testicular tumor are very serious. In particular, agranulocytosis in bone marrow suppression may be life threatening. In this study, we examined opportunistic infectious diseases and preventive counter measures in the compromised conditions of anti-cancer drug chemotherapy. The patients underwent anti-cancer drug chemotherapy with PBCST for the treatment of intractable testicular tumors at Kobe University Hospital from September 1996 to September 2002. The high-dose chemotherapy regimen consisted of total doses per course of 1,250 mg/m2 carboplatin, 1,500 mg/m2 etoposide, and 7,500 mg/m2 ifosfamide. Twenty-four men (median age, 30 years; range, 18-70 years) received 50 courses of chemotherapy in total. The nadir of peripheral leukocyte counts was less than 1,000/mm3 in all courses, and the mean period was for 7.1 days. None of these patients developed critical sepsis leading to disseminated intravascular coagulation or treatment-related death. Our detailed data show that we can perform high-dose anti-cancer drug chemotherapy with PBSCT for intractable testicular tumors without serious infectious complications if we take sufficient preventive countermeasures for infectious diseases.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.     

Testis germ cell tumours: which chemotherapy, for which patients?

Germ cell tumours of the testis are curable disease. Two different pathological subtypes are observed: seminoma and non-seminoma. Two tumour stages have been defined: the disease limited to the testis and the advanced disease. In the latter group, the prognosis is established by a specific classification based on the level of serum tumour marker and the location of the metastases. The most active first line chemotherapy is a combination of bleomycine, etoposide and cisplatine. Patients with good prognostic factors receive three cycles of this regimen; patients with poor-risk characteristics receive four cycles of the same regimen. The strategy in non-seminoma patients is to give a first-line chemotherapy adapted to the risk factors, then to complete surgical exeresis of all residual disease. Patients with stage I disease may receive two cycles of the same regimen. The strategy for advanced seminoma is to give first-line good-risk chemotherapy followed by a close observation and in several selected cases a surgical removal of all residual disease. Patients with stage I disease may receive one cycle of carboplatin. Salvage chemotherapy is based on the combination of ifosfamide, cisplatine and either vinblastine or paclitaxel.     

The contemporary role of chemotherapy for advanced testis cancer: a systematic review of the literature

Context

Germ cell tumours (GCTs) of the testis are the most common cancer in young men; they are also one of the most curable cancers. Standard treatment of metastatic GCTs has evolved on the basis of randomised trials and prognostic factors.

Objective

This review summarises the evolving role of chemotherapy in the treatment of previously treated and untreated patients with metastatic GCTs and outlines the current standard treatment.

Evidence acquisition

Randomised and nonrandomised trials of first-line, salvage, and palliative therapy were reviewed.

Evidence synthesis

Three cycles of standard bleomycin, etoposide, and platinum (BEP) can be considered the gold-standard treatment in good-risk patients, and four cycles of the same combination can result in cure in approximately 80% of intermediate-risk and 50% of poor-risk patients. The routine use of high-dose chemotherapy in patients with intermediate- or poor-prognosis GCT has not improved treatment outcome, but the role of tumour marker decline during the first cycles may provide useful prognostic information. Prognostic variables in patients who experience treatment failure after cisplatin-based chemotherapy can be used to guide salvage strategies, and many new drugs or combinations have shown activity in this setting. Patients and physicians should be aware of the risk of short- and long-term toxicity of treatments, and guidelines for screening and prevention of this risk should be established.

Conclusions

A risk-based strategy offers the best chance of cure, even in patients with refractory GCT.     

Two-step ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer: a case report]

A 35-year-old male had advanced nonseminomatous germ cell tumor (stage IIIC, embryonal cell carcinoma) which proved refractory to conventional PVB combined chemotherapy. He was then treated with an ultra high-dose chemotherapy consisting of carboplatin (1.5 g/m2) and etoposide (1.3 g/m2), followed by the transplantation of peripheral blood stem cells (PBSCT) with a total of 1.9 x 10(5)/kg granulocyte colony-forming cells (CFU-GM). Because he developed lung metastasis, escalated doses of carboplatin (2.0 g/m2), and etoposide (1.8 g/m2) combined with cyclophosphamide (7.0 g/m2) were given with peripheral blood stem cell transplant of 3.2 x 10(5)/kg CFU-GM. He has remained free of any recurrence without maintenance therapy.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

Between June 1998 and August 2000, five patients with germ cell tumor were treated with high-dose CEI: carboplatin (1,250 mg/m2), etoposide (1,500 mg/m2), and ifosfamide (7.5 g/m2), followed by peripheral blood stem cell transplantation (PBSCT) at Yokohama City University Hospital. All patients were classified into either poor risk group of International Germ Cell Consensus Classification or advanced extent of Indiana University stage, and received one cycle of high-dose CEI after 4-6 cycles of standard PEB (cisplatin, bleomycin, vinblastin) therapy. Three of the patients achieved complete response, one achieved partial response and one achieved no change after whole treatment. There were no fatal complications and no treatment-related deaths.