BEP (bleomycin, etoposide, cisplatin) therapy for testicular tumors]

We describe our experience with BEP (bleomycin, etoposide, cisplatin) therapy as chemotherapy for testicular tumors in 11 patients. Eight were non-seminomatous testicular cancer patients and 3 were seminoma patients. Three of 8 non-seminomatous testicular cancer patients had no evident metastasis and BEP therapy was performed for prophylaxis of recurrence. Other 5 non-seminomatous testicular cancer patients and 3 seminoma patients had metastatic lesions and BEP therapy was performed to cure these metastatic lesions. Ten of our 11 patients are living and disease-free. One non-seminomatous testicular cancer patient who had brain, lung, eye and bladder metastases and had an extremely elevated human chorionic gonadotropin (hCG) level responded only partially and died later due to disease progression. Side effects in most patients were nausea, vomiting, alopecia and leucopenia and all these side effects were reversible. Neuromuscular toxicity such as paresthesia or abdominal cramp that is sometimes encountered in PVB (cisplatin, vinblastine, bleomycin) therapy was not seen in our patients. Our results support the concept that BEP therapy is better than PVB therapy as an initial chemotherapy for testicular tumors.     

The result of VIP chemotherapy as an induction therapy in 6 patients with non-seminomatous extragonadal germ cell tumor

We treated 6 patients with non-seminomatous extragonadal germ cell tumor (NSEGCT) by VP-16 + ifosfamide + cisplatin (VIP) chemotherapy as an induction therapy to investigate the effectiveness and safety. Primary lesions were located at the mediastinum in 4 patients and the retroperitoneum in 2 patients. As a rule, all patients were treated with VIP chemotherapy of 4 courses with or without second-line treatment such as chemotherapy, residual tumor resection and/or radiation. Following the induction therapy (VIP), 4 of 6 patients (67%) achieved complete or partial responses. After salvage therapy, 4 patients (67%) achieved complete responses and two other patients also achieved partial responses. However, only 2 of the 5 patients who had been follow-up for more than 2 years have remained disease free. The effects of VIP chemotherapy on non-seminomatous extragonadal germ cell tumor appeared to be similar to those of the conventional chemotherapies though the number of patients was small in the current study. It appears to be necessary to design more effective regimen.     

Successful combination chemotherapy (cisplatinum, vinblastine, and bleomycin) against peritoneal dissemination of intracranial germ cell tumor

We found combination chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB therapy) effective in the treatment of a patient with a pineal germ cell tumor with peritoneal dissemination. The metastatic complication may have been attributable to the ventriculoperitoneal shunt tube. After the first course of PVB therapy, the disseminated tumors were decreased in size; no residual tumors were detected after the third course by laparoscopic examination, computed tomographic scanning, or echogram. Our results suggest that combined PVB therapy is effective in the treatment of extraneural metastasis from intracranial germ cell tumors.     

High-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced extragonadal germ cell tumor--a case report]

We reported the experience of high-dose chemotherapy (HDC) combined with peripheral stem cell transplantation (PBSCT) in 29 years-old man with advanced retroperitoneal germ cell tumor accompanied with left supraclavicular lymph node metastases, who obtained complete remission after comprehensive treatment. The initial levels of serum AFP, hCG and beta-hCG were high at 30.2 ng/ml, 14,000 mIU/ml and 66 ng/ml, respectively. After 3 courses of chemotherapy (BEP regimen), while left supraclavicular lymph node swelling was disappeared, the retroperitoneal mass lesion persisted on CT scan. Not all of 3 markers fell to the normal range. After myelosuppressive chemotherapy (etoposide 500 mg/m2 Day 1-3), PBSCs were collected by two consecutive apheresises on Day 17 and 18. In total, 19.5 x 10(6)/kg CD 34 positive cells were obtained. The patient underwent PBSCT (all CD 34 positive cells were infused) on Day 0 following HDC (CBDCA 250 mg/m2/day, etoposide 300 mg/m2/day, IFM 1.5 g/m2/day, Day-7(-)-3, respectively). He became severely leukopenic and thrombopenic with nadir of 200/microliter on Day 6 and 2 x 10(4)/microliter on Day 2, respectively. By administration of platelet transfusion and G-CSF, the white blood cell counts and thrombocyte counts recovered to 6,400/microliter and 4.1 x 10(4)/microliter on Day 10, respectively. Microbiologically enterocolic and respiratory tract infections occurred with elevated body temperature (> 40 degrees C). Antibiotic and antimycotic treatments were continued until disappearance of all clinical and microbiological evidence. He was kept for 10 days in clean room. After HDC, all markers fell to the normal range, but the retroperitoneal residual mass still persisted. Resection of the residual mass and retroperitoneal lymph node dissection were performed with pathological examination revealing tissue necrosis without viable cell. The patient has survived with no sign of the disease for 9 months.     

A case report of extragonadal germ cell tumor with retroperitoneal origin]

A case of extragonadal germ cell tumor is reported. A 41-year-old man, an elementary school teacher, was referred to our department with left abdominal pain and gynecomastia on September, 1985. Laboratory examinations revealed markedly high levels of LDH, AFP and HCG-beta. IVP and abdominal CT disclosed dislocation of the left kidney and the large left retroperitoneal mass. The mass was supplied by the left lumbal arteries on the aortogram. Chest X-ray film showed multiple coin lesions in the bilateral lung fields. By percutaneous needle biopsy, the histological finding of the tumor showed choriocarcinoma. No abnormal findings were found in either testicle by the physical and ultrasonic examinations. This case was diagnosed as extragonadal choriocarcinoma with lung metastasis. After 3 courses of chemotherapy (PVB regimen), resection of the retroperitoneal residual mass and lymphadenectomy were performed. Postoperatively, the chemotherapy, CISCA II - VB IV regimen, was repeated. The patient was discharged after 7 months hospitalization. Now, 35 months after operation, tumor markers, chest X-ray and abdominal CT showed no evidence of recurrence of the tumor.     

Treatment results of VIP (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy in metastatic germ cell tumors

PURPOSE: We investigated the effectiveness and toxicity of VIP therapy as a first-line chemotherapy for patients with metastatic germ cell tumor. PATIENTS AND METHODS: From March 1994 to October 1997, we treated 16 patients with VIP therapy consisting of etoposide (100 mg/m2), ifosfamide, (1.2 g/m2) and cisplatin (20 mg/m2), all of which were generally given daily for 5 consecutive days every 3 weeks. Of the 16 patients, 6 were classified into a good, 5 into an intermediate, and 5 into a poor prognostic group according to the International Germ Cell Consensus Classification. RESULTS: Thirteen patients (81%) achieved complete response with VIP alone or VIP plus surgery. Three-year survival rate was 100% in good and intermediate prognostic group, while 40% in poor prognostic group. Although all patients had Grade 3 or higher myelosuppression, the treatment was well tolerated and no patient died of treatment-related complications. CONCLUSIONS: VIP appears to be an effective and safe regimen as an induction chemotherapy for good and intermediate risk patients with germ cell tumor. However, more intensive regimen may be necessary for poor-risk patients.     

A case of extragonadal germ cell tumor with inferior vena caval tumor thrombus]

We report a case of retroperitoneal extragonadal germ cell tumor with tumor thrombus in the inferior vena cava. The patient referred to our hospital with lumbago. Computed tomography (CT) showed a bulky mass in the retroperitoneum. The levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-HCG) in the serum were elevated. Histological examinations indicated embryonal cell carcinoma. Bilateral testicles did not contain any palpable mass upon careful palpation. No tumor mass was detected in the bilateral testicles on ultrasonography. Clinically, the diagnosis was a retroperitoneal extragonadal germ cell tumor associated with para-aortic lymph-node involvement. After the combination chemotherapy (BEP 1 course and EP 3 courses), the tumor mass was reduced in size and the tumor marker was normalized. Retroperitoneal lymph node dissection (RPLND) was performed and tumor thrombus in the inferior vena cava was resected. There was no involvement of the viable cells in the resected tumor. The patient has been in good condition with no evidence of disease.     

Pediatric extragonadal germ cell tumor of the scalp

Extragonadal germ cell tumors are relatively rare tumors, accounting for 5% to 10% of all germ cell tumors in adults. In children, approximately two thirds of germ cell tumors are extragonadal. Extragonadal germ cell tumor of the scalp is exceedingly rare. The authors report the case of a 1(1/2)-year-old boy with extragonadal germ cell tumor over the occipital region. Examination of the chest, abdomen, and gonads was normal. Computed tomography scan of the head showed a large, well-defined, lobulated, heterogeneously enhancing soft tissue mass lesion in the occipital region. The underlying bone was normal with no evidence of intracranial extension. Biopsy results of the scalp mass showed features consistent with embroynal carcinoma. Serum alpha-fetoprotein (AFP) level was elevated. The child was started on chemotherapy and received 4 cycles of cisplatin, etoposide, and bleomycin (PEB). There was more than 90% reduction in the size of the mass at the end of the fourth cycle. The residual mass was excised and followed up with 2 cycles of postoperative PEB. Ten months after excision the patient is well, without recurrence, and the AFP level is normal.     

Diagnostic difficulties before definitive treatment of an extragonadal retroperitoneal germ cell tumor

A primary extragonadal germ cell tumor of the retroperitoneum was diagnosed in a 47-year-old man without elevated serum alpha-fetoprotein, human chorionic gonadotropin, or lactate dehydrogenase levels. The diagnosis was made by histologic analysis after resection. The patient responded well to a combination of cisplatin, etoposide, and ifosfamide, achieving a partial response with four cycles. Residual tumor resection revealed necrotic tissue only. The patient was alive and disease free 24 months after diagnosis. The diagnostic difficulties of this particular situation are discussed.     

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.     

Adjuvant chemotherapy (MVP-CAB; methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin) for bladder cancer]

Twenty-three patients with bladder cancer (TCC; 18 patients, SCC; 5 patients) were treated with adjuvant chemotherapy (day 1: methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, bleomycin 30 mg, day 2: cisplatinum 50 mg/m2; MVP-CAB). A total of 3 cycles of MVP-CAB were given as preoperative or postoperative therapy. The following results were obtained. Group 1 (purpose to preserve the bladder, preoperative MVP-CAB): Four of 7 patients achieved a partial response. It was possible to perform bladder preservation surgery in 3 of these 4 patients. All 3 patients had pedunculated, solitary tumors, and there was no carcinoma in situ. Group 2 (purpose to improve the prognosis; preoperative MVP-CAB): Hydronephrosis did not resolve in the 4 patients with this complication. They received total cystectomy, and 2 patients died of cancer 23 months later. Group 3 (purpose to improve the prognosis; postoperative MVP-CAB): Ten of 12 patients (total cystectomy; 10 patients, partial cystectomy; 2 patients) survived disease-free for an average of 17 months (5-44 months), 1 patient developed recurrence 12 months later, and 1 patient died of cancer 6 months later. The 1-year survival rate in Group 3 was 86% for TCC, 100% for SCC, 80% for grade 3 TCC, and 89% for pT2 or more advanced cancer.     

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.     

Combination chemotherapy with methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin (MVP-CAB) for metastatic urothelial cancer]

We studied 31 patients with bidimensionally measurable metastases of urothelial cancer who were treated with a planned regimen (20 mg/m2 methotrexate, 0.6 mg/m2 vincristine, 500 mg/m2 cyclophosphamide, 20 mg/m2 adriamycin, and 30 mg bleomycin on day 1, and 50 mg/m2 cisplatinum on day 2) in cycles given every 3 weeks. CR was achieved in 4 patients (13%) and PR in 17 patients (55%). The response rates according to the disease characteristics were 71% for TCC, 33% for SCC, 67% for renal pelvis tumors, 67% for bladder tumors, 73% for lung metastases, 67% for liver metastases, and 67% for lymph node metastases. The median response duration and the number of cycles of therapy were 32 months/3 cycles for patients with a CR and 6 months/6 cycles for those with a PR. The median duration of survival was 32 months (range: 3-46) in CR, 11 months (range: 1-37) in PR, and 6 months (range: 2-10) in non responders (NC + PD). A significant prolongation of survival was noted in patients with either CR (p less than 0.01) or PR (p less than 0.05). Then main toxic effects were pulmonary fibrosis and myelosuppression. Two patients aged 73 and 81 died of pulmonary fibrosis. However, it was possible to prevent pulmonary fibrosis by not administering bleomycin to patients over 70 years of age, or to patients with pulmonary dysfunction. WBC count nadirs of less than 2,000/m3 were noted in 22 patients (71%). Platelet count nadirs of greater than 5 x 10(4)/mm3 were noted in 7 patients (23%). However, there were no deaths due to myelosuppression.     

A case report of extragonadal germ cell tumor with special reference to VAB-6 therapy

A 24-year-old man with a large abdominal mass in addition to the left lymph node swelling was referred to our clinic. Neither testicular nodulus nor overt evidence of tumor development in the scrotal cavity was confirmed by careful palpation and testicular biopsy. Values of lactate dehydrogenase, alpha-fetoprotein, human chorionic gonadotropin (HCG) and beta-HCG in the serum were markedly elevated. The specimen removed from the left cervical lymph node demonstrated mixed type of choriocarcinoma and embryonal carcinoma. A partial response near complete remission was achieved following the VAB-6 combination therapy (cyclophosphamide, vinblastine, actinomycin D, bleomycin, cis-platinum). The patient has been in good health with normal tumor markers and abdominal CT findings.     

Retroperitoneal extragonadal germ cell tumor presenting as a bulky pelvic mass of the obturator fossa

Extragonadal germ cell tumors (EGGCT) are commonly found in the midline of the body. We report a rare case of a retroperitoneal EGGCT presenting as a bulky pelvic mass located between the left internal and external iliac arteries in a 29-year-old man. His alpha-fetoprotein level was 12946.2 ng/mL and the biopsy of the tumor revealed a nonseminomatous germ cell tumor. After three cycles of chemotherapy (bleomycin/etoposide/cisplatin) followed by resection of all residual tumors, one cycle of salvage chemotherapy (etoposide/ifosphamide/cisplatin) was added. The patient was disease free at 21-month follow up.     

Anti‐Ma2 paraneoplastic encephalitis associated with testicular germ cell tumor treated by carboplatin,etoposide and bleomycin

Anti‐Ma2‐associated encephalitis is a paraneoplastic disorder that predominantly affects the limbic system, diencephalon and brainstem, and is usually associated with tumors of the testis. We report a 35‐year‐old man with a right testicular mass who presented with multiple neurological complains, and clinical, serological and radiological features compatible with anti‐Ma2‐associated encephalitis. After three courses of carboplatin, etoposide and bleomycin for metastatic testicular germ‐cell tumor, all elevated tumor markers normalized and the retroperitoneal metastases disappeared, but the neurological disorder deteriorated. To our knowledge, this is the first case in which orchiectomy followed by carboplatin, etoposide and bleomycin for a testicular tumor with anti‐Ma2 encephalitis was performed.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Treatment of metastatic germ cell tumors with etoposide and cisplatin as first line chemotherapy

PURPOSE: The efficacy and toxicity of two-drug therapy (etoposide and cisplatin, EP) in patients with metastatic germ cell tumors were investigated. PATIENTS AND METHODS: Between December 1996 and November 1999, 18 patients with metastatic germ cell tumors (6 seminomas and 12 non-seminomas, Stage II 8, Stage IIIA 2, Stage IIIB 6, Stage IIIC 2) were treated by 3-5 cycles of induction chemotherapy regimen (EP). Etoposide and cisplatin were administrated in doses of 100 mg/m2 and 20 mg/m2, respectively, on days 1 to 5 and then repeated from day 21. After tumor markers obtained normal levels, one or two additional cycles of EP were continued. Patients showing evidence of residual tumor mass underwent debulking surgery as early as possible. RESULTS: At the end of EP therapy, 4 (22%) of the 18 patients achieved complete remission and 14 patients (78%) showed partial remission. Seven patients of partial remission were treated by excision of residual abnormalities: 6 had pathologically necrotic debris in the resected specimen and 1 had teratoma, and these 7 patients all achieved complete remission. Four other patients achieving partial remission were followed without surgical excision and have had no evidence of disease progression. Remaining three patients achieving partial remission received salvage chemotherapy with or without adjunctive surgery, resulted in complete remission in 2 patients and partial remission in 1 patient. EP demonstrated to have less treatment-related toxicity compared with that of EBP. Follow up studies ranging from 12 to 47 months (median, 29.6) showed that one patient experienced a relapse from complete remission at 13 months and was salvaged by chemotherapy and surgery. Finally, thirteen patients (72%) who achieved complete remission are alive and disease-free and 5 patients (28%) showing partial remission are alive with negative tumor markers and no evidence of relapse. CONCLUSION: These results suggests that EP is an efficacious and less toxic first line regimen for good-prognosis patients with metastatic germ cell tumors.     

Primary extragonadal germ cell tumor of the prostate in a young man

We report on a case of malignant prostatic teratoma treated with radical cystoprostatectomy and cisplatin-based chemotherapy because of intraoperative tumor rupture. During chemotherapy the patient suffered acute myocardial infarction and was treated with percutanous coronarangiography and stenting.     

Surgery of large residual mass after chemotherapy in advanced testicular germ cell tumor

Treatment for testicular tumours has progress in such a manner in the last years that high cure percentages can at present be achieved. After chemotherapy, in most cases, residual mass can appear. In this cases surgery is considered a viable therapeutic option although it implies an advanced surgical training since it is a complex technique and implies serious implications. We submit the case of a patient who presented a large residual mass from a testicular germ cell tumour after being treated with orquiectomía and chemotherapy. Surgery was performed resulting in total and radical extirpation of residual mass.