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Hinyokika Kiyo. Acta Urologica Japonica Mar 2011Bleomycin, etoposide and platinum (BEP) therapy is used on patients with metastatic germ cell cancer but approximately 20-30% of these patients fail to achieve a durable... (Review)
Review
Bleomycin, etoposide and platinum (BEP) therapy is used on patients with metastatic germ cell cancer but approximately 20-30% of these patients fail to achieve a durable complete response following the administration of BEP therapy. For such patients, salvage chemotherapy is subsequently considered. Although either VIP of VeIP therapy had been tended to be selected as salvage chemotherapy, recent studies have suggested two novel strategies as an alternative to conventional regimen for salvage chemotherapy. One is high-dose chemotherapy, while the other is the use of a regimen containing newly developed chemotherapeutic agents. In this study, we summarize the current status of therapeutic strategy for patients with metastatic germ cell cancer refractory to BEP therapy, and then present the experience with salvage chemotherapy at our institution.
Topics: Humans; Male; Neoplasms, Germ Cell and Embryonal; Prostatic Neoplasms; Salvage Therapy
PubMed: 21586892
DOI: No ID Found -
Journal of Ovarian Research Apr 2021Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought... (Review)
Review
BACKGROUND
Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis.
CASE PRESENTATION
A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma.
CONCLUSION
Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.
Topics: Adult; Choriocarcinoma; Female; Humans; Neoplasm Metastasis; Ovarian Neoplasms; Prognosis
PubMed: 33888146
DOI: 10.1186/s13048-021-00810-3 -
Anti-cancer Drugs Apr 2016A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a...
Metastatic testicular cancer presenting with liver and kidney dysfunction treated with modified BEP chemotherapy combined with continuous hemodiafiltration and rasburicase.
A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a huge liver mass, and multiple lung masses, although there was no enlarged retroperitoneal lymph node swelling. Laboratory tests showed severe liver and kidney dysfunction and high levels of serum α-fetoprotein (11,997 ng/ml). Although needle biopsies of the testicular and liver masses were performed, the tissues were insufficient for a pathological diagnosis. As liver and kidney function worsened, we started chemotherapy with bleomycin, etoposide, and cisplatin (BEP chemotherapy), which was modified because of the liver and renal dysfunction. We also used continuous hemodiafiltration and rasburicase to prevent tumor lysis syndrome. After induction of chemotherapy, the liver and kidney dysfunction improved immediately and the high orchiectomy was performed on day 8 after chemotherapy. The pathological diagnosis was a yolk sac tumor. He underwent four courses of the BEP regimen and five courses of the TIN regimen (paclitaxel, ifosphamide, and nedaplatin), followed by the resection of liver metastases. There was no evidence of viable cells in the resected liver and no recurrence was evident at 1 year postoperatively.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Endodermal Sinus Tumor; Etoposide; Hemodiafiltration; Humans; Kidney Diseases; Liver Diseases; Male; Neoplasm Metastasis; Testicular Neoplasms; Tumor Lysis Syndrome; Urate Oxidase
PubMed: 26736135
DOI: 10.1097/CAD.0000000000000334 -
Biomedicine & Pharmacotherapy =... Jun 2021There is growing concern that some cytotoxic regimens for cancer adversely affect spermatogenesis and male fertility. Increasing evidence demonstrated that melatonin has...
There is growing concern that some cytotoxic regimens for cancer adversely affect spermatogenesis and male fertility. Increasing evidence demonstrated that melatonin has beneficial impacts on reproductive processes; however, whether melatonin can protect against bleomycin, etoposide, and cisplatin (BEP) chemotherapy regimen-induced testicular toxicity, remains obscure. The present study aimed to explore the effect of melatonin on BEP-evoked testicular injury in rats. Adult male Wistar rats (n = 10/group) were intraperitoneally (i.p.) injected with one cycle of 21 days of 0.33 therapeutically relevant dose levels of BEP (.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin) with or without melatonin. At the end of the study, sperm parameters, testosterone level, stereology of testes, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), the expression of apoptosis-associated genes such as Bcl2, Bax, Caspase-3, p53, and TNF-α (Real-time PCR and Immunohistochemistry) were evaluated. Our findings showed that melatonin restored spermatogenesis by improving sperm count, motility, viability, and morphology. Testosterone level, histopathology, and stereology of testes were significantly improved in melatonin-administrated groups. Furthermore, melatonin recovered the oxidative status of the testes through elevating TAC and ameliorating MDA and NO levels. More importantly, melatonin therapy suppressed BEP-evoked apoptosis by modulating Bcl-2, Bax, Caspase-3, p53, and TNF-α expression in testes. In conclusion, melatonin protects the testes against BEP-induced testicular damage by attenuating nitro-oxidative stress, apoptosis, and inflammation, which provides evidence for melatonin as a possible clinical therapy against BEP-associated gonadotoxicity and male sub/infertility.
Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Bleomycin; Cisplatin; Cytoprotection; Dose-Response Relationship, Drug; Etoposide; Male; Melatonin; Oxidative Stress; Rats; Rats, Wistar; Testis
PubMed: 33752059
DOI: 10.1016/j.biopha.2021.111481 -
South Asian Journal of Cancer Apr 2021Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be...
Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be salvaged with systemic therapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Complete remission can be obtained in approximately 50 to 60% of patients treated with HDCT. Our experience reports the efficacy and safety of HDCT followed by ASCT in relapsed GCT. Analysis of patient records (2012-2019) showed that three patients had received HDCT and ASCT. All the three patients were treated with BEP (bleomycin, etoposide, and cisplatin) as first-line therapy. HDCT was done in Case 1 after third-line salvage and in other two patients after second-line salvage chemotherapies. High-dose carboplatin and etoposide were used as conditioning regimen. Granulocyte colony-stimulating factor was used for the mobilization of stem cells. After ASCT, complete remission was documented in all the patients. All were alive and disease-free till the last follow-up. Grade ¾ toxicities including myelosuppression, diarrhea, and mucositis were observed in all three patients. This is the first report from India on HDCT with ASCT in GCT. HDCT/ASCT seems to be feasible, safe, and effective in relapsed testicular GCTs.
PubMed: 34568223
DOI: 10.1055/s-0041-1731516 -
American Society of Clinical Oncology... 2014Approximately 20% to 40% of patients with germ-cell tumors (GCT) will need advanced medical treatment because of relapse or initial metastatic disease. The survival and... (Review)
Review
Approximately 20% to 40% of patients with germ-cell tumors (GCT) will need advanced medical treatment because of relapse or initial metastatic disease. The survival and recommended treatment for men with metastatic disease varies according to histology, primary and metastatic sites, and the level of prechemotherapy tumor markers. For patients with a good prognosis, three cycles of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide, and cisplatin are recommended. For patients with intermediate- and poor prognosis, four cycles of bleomycin, etoposide, and cisplatin remains the preferred treatment option, although a switch to a more intensive regimen can be considered a new alternative. A major advance in salvage therapy for GCT in the last 5 years was the development of a new risk classification system. Initial salvage treatment includes both high-dose chemotherapy and standard-dose chemotherapy. There is clear consensus that patients with residual masses larger than 1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND); however, the role of PC-RPLND in patients with serologic and radiographic complete response to first-line chemotherapy is controversial. The rationale for PC-RPLND in patients with small residual masses is discussed, and only a small minority of advanced nonseminoma GCT (NSGCT) patients are suitable candidates for observation after first-line chemotherapy. Post-treatment long-term toxicity has emerged as an important issue for GCT survivors. Examples of late effects are secondary nongerm-cell cancers and cardiovascular disease, which represent the most severe and potentially life-threatening effects of cancer treatment. Follow-up of cancer survivors should include recommendations for maintaining a healthy lifestyle to reduce the risk of serious long-term and late effects of treatment.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Humans; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Neoplasms, Germ Cell and Embryonal; Retroperitoneal Neoplasms; Treatment Outcome; Young Adult
PubMed: 24857101
DOI: 10.14694/EdBook_AM.2014.34.e180 -
Journal of B.U.ON. : Official Journal... 2016One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in...
A phase II single institution single arm prospective study with paclitaxel, ifosfamide and cisplatin (TIP) as first-line chemotherapy in high-risk germ cell tumor patients with more than ten years follow-up and retrospective correlation with ERCC1, Topoisomerase 1, 2A, p53 and HER-2 expression.
PURPOSE
One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in first-line of the paclitaxel-ifosfamide-cisplatin combination (TIP) in HRGCT patients and tried to identify biomarkers that may allow patient-tailored treatments.
METHODS
Between October 1997- September 2000, 28 chemo-naive HRGCT patients were enrolled. Patients received 4 cycles of TIP (paclitaxel 175 mg/m(2) day 1/; ifosfamide 1.2 g/m(2)/day, days 1-5; Mesna 1.2 g/m(2)/day, days 1-5; and cisplatin 20 mg/m(2)/day, days 1-5 every 3 weeks). A non-randomized comparison was made between HRGCT patients treated in the same period with first-line TIP and bleomycin-etoposide-cisplatin (BEP) (28 patients vs 20). In 17 HRGCT patients treated between 1998-2006, ERCC1, Topoisomerase 1 and 2A, p53 and HER-2 expression was retrospectively analysed by immunohistochemistry (IHC) (7 patients with TIP, 10 with BEP), and correlations were made with response to chemotherapy and survival.
RESULTS
With a median follow-up of 72 months [range 48+...89+], 5-year disease free survival (DFS) was 55%, with 95% CI 36-72, and the overall survival (OS) was 63%, with 95% CI 44-78. In June 2015, with a median follow-up of 196.47 months (range 177.30-209.27) (>15 years), 12 [%?] patients were alive and disease-free, and 16 [%?] had died (12 specific causes). There was no significant correlation between the expression of ERCC1, Topoisomerase 1 and 2A, HER-2 and p53 and response to treatment.
CONCLUSION
Long-term follow-up showed no difference in OS between TIP vs BEP as first-line therapy. Both regimens had mild toxicity.
Topics: Adult; Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; DNA-Binding Proteins; Endonucleases; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Prospective Studies; Receptor, ErbB-2; Retrospective Studies; Testicular Neoplasms; Tumor Suppressor Protein p53
PubMed: 27569093
DOI: No ID Found -
Onkologie Jun 2007
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cause of Death; Cisplatin; Etoposide; Humans; Male; Neoplasms, Germ Cell and Embryonal; Pneumonia; Positron-Emission Tomography; Prognosis; Respiratory Function Tests; Testicular Neoplasms
PubMed: 17551251
DOI: 10.1159/000102516 -
Asian Pacific Journal of Cancer... 2012Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in...
INTRODUCTION
Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes.
METHODS AND MATERIALS
Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 and D15 and either etoposide 100mg/m2 IV D1- D5 and cisplatin 20mg/m2 IV D1- D5 (5 day BEP regimen) or etoposide 165 mg/m2 D1- D3 and cisplatin 50mg/m2 D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed.
RESULTS
Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites.
CONCLUSION
It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Disease-Free Survival; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Malaysia; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Survival Rate; Treatment Outcome; Young Adult
PubMed: 22938405
DOI: 10.7314/apjcp.2012.13.6.2467 -
Annals of Oncology : Official Journal... Nov 2014SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP)....
BACKGROUND
SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results.
PATIENTS AND METHODS
In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study.
RESULTS
At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%.
CONCLUSIONS
The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemotherapy, Adjuvant; Cisplatin; Etoposide; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Testicular Neoplasms
PubMed: 25114021
DOI: 10.1093/annonc/mdu375