Bleomycin, Etoposide, Cisplatin Chemotherapy Research Articles

Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in conservative treatment of malignant ovarian germ cell tumor: a multicenter and retrospective study (096)

Objectives: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (TC) chemotherapy regimens on fertility and prognostic outcomes among patients with malignant ovarian germ cell tumor (MOGCT) who received fertility-sparing surgery (FSS). Methods: The study included 213 women with MOGCT who underwent FSS. We performed a 3:1 propensity score matching between the BEP and TC groups. The Chi-square test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS), and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factors of DFS. Results: A total of 185 (86.9%) patients underwent BEP chemotherapy, and 28 (13.1%) patients underwent TC chemotherapy. The median age was 22 years (range: 8-44 years), and the median follow-up was 63 months (range: 1-191 months). Fifty-one (29.3%) patients had a pregnancy plan, 43 (84.3%) patients got pregnant, and 35 (81.4%) patients delivered successfully. Fourteen (6.6%) patients experienced recurrence, and four (1.9%) patients died. In the before and after matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during pregnancy status, and live birth between BEP and TC groups (p >0.05). Also, there were no significant differences in DFS and OS between BEP and TC groups (p >0.05). The clinical staging is the only risk factor of postoperative recurrence (HR: 21.3, p <0.001). Conclusions: There was no significant difference between the effects of BEP and TC regimens on the fertility and prognosis of MOGCT patients who received FSS. The TC regimen seems to be a viable alternative to the BEP regimen for MOGCT patients. Objectives: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (TC) chemotherapy regimens on fertility and prognostic outcomes among patients with malignant ovarian germ cell tumor (MOGCT) who received fertility-sparing surgery (FSS). Methods: The study included 213 women with MOGCT who underwent FSS. We performed a 3:1 propensity score matching between the BEP and TC groups. The Chi-square test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS), and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factors of DFS. Results: A total of 185 (86.9%) patients underwent BEP chemotherapy, and 28 (13.1%) patients underwent TC chemotherapy. The median age was 22 years (range: 8-44 years), and the median follow-up was 63 months (range: 1-191 months). Fifty-one (29.3%) patients had a pregnancy plan, 43 (84.3%) patients got pregnant, and 35 (81.4%) patients delivered successfully. Fourteen (6.6%) patients experienced recurrence, and four (1.9%) patients died. In the before and after matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during pregnancy status, and live birth between BEP and TC groups (p >0.05). Also, there were no significant differences in DFS and OS between BEP and TC groups (p >0.05). The clinical staging is the only risk factor of postoperative recurrence (HR: 21.3, p <0.001). Conclusions: There was no significant difference between the effects of BEP and TC regimens on the fertility and prognosis of MOGCT patients who received FSS. The TC regimen seems to be a viable alternative to the BEP regimen for MOGCT patients.

Transcriptome modulation following administration of luteolin to bleomycin-etoposide-cisplatin chemotherapy on rat LC540 tumor Leydig cells.

Leydig cell tumours represent 1%-3% of all cases of testicular tumours in men. Such tumours respond poorly to radiation or chemotherapy, including bleomycin-etoposide-cisplatin (BEP) combinatorial therapy. In this study, we investigated an alternative approach involving luteolin to improve the efficacy of chemotherapy. LC540 tumour Leydig cells were treated with BEP (bleomycin 40µg/ml, etoposide 4µg/ml, cisplatin 8µg/ml) and/or luteolin 10µM for comparison with DMSO-treated cells. We performed a transcriptome analysis using RNA-Seq to characterise changes in biological processes and signalling pathways. Treatments of LC540 tumour Leydig cells with luteolin significantly decreased the expression of genes involved in cholesterol biosynthesis, while increasing the expression of genes related to glutathione conjugation (p<.05). Genes being significantly upregulated in response to BEP treatment were involved in the response to toxic substances and transcriptional regulation. Oppositely, genes being significantly downregulated by BEP treatment were enriched for intracellular signal transduction, cell migration, cell adhesion, reproductive system development and cholesterol biosynthesis. BEP chemotherapy proved to be effective in increasing gene expression related to apoptosis of tumour Leydig cells. However, addition of luteolin to BEP treatment had no other effects on biological processes or pathways related to cancer treatment.

NCOG-61. A CASE OF LONG TERM SURVIVOR OF DISSEMINATED AND RELAPSED GERMINOMA. EIGHTEEN YEARS OF FOLLOW UP

Abstract Germinomas will respond to first-line treatment in general, but prognoses of disseminated and/or relapsed disease are sometimes poor and detailed course of those patients are not well documented. Here we report one of such cases. PATIENT: A 35-year-old man (at the time of abstract submission) initially had polyuria at the age of 15 and anorexia at 16. At the age of 17, MRI showed neurohypophyseal and disseminated tumor along lateral ventricular walls. He was diagnosed to have germinoma by partial resection of the tumor. ICE (Ifosfamide, Cisplatin, Etoposide) chemotherapy was given followed by 24 Gy whole ventricular irradiation. The tumor was well controlled for 22 months. However despite maintenance ICE chemotherapy, the tumor relapsed along the ventricular walls. With simultaneous BEP (Bleomycin, Etoposide, Cisplatin) chemotherapy and 40 Gy whole neuroaxis irradiation, all the tumor disappeared and he remains in complete remission now. He is receiving hormone replacement therapy. Eight years after the initial surgery, an MRI showed cavernous angioma in the cerebellum and the number has been increasing in follow-up scans. Asymptomatic minor bleeding occurred 14 and 15 years after the initial surgery. On MRA, no vasculopathy on major vessels has been identified. His wife gave birth to his first child through infertility treatment, when he was 34. He finished graduate school to obtain master degree and working as a company employee. CONCLUSION: Germinoma is a disease that can cause long-term survival even after recurrence. However, complications may occur and multimodality approaches are needed for the survivors.

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS425 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a favourable response, and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in the favourable response rate and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 13 sites open in UK (led by Cambridge Clinical Trials Unit), 67 sites open in the USA (led by Children’s Oncology Group). As of September 2019, 98 patients have been recruited triggering the first formal interim analysis. Clinical trial information: NCT02582697.

Surveillance in stage I MOGCTs (malignant ovarian germ cell tumors): A MITO prospective study (multicenter Italian trials in ovarian cancer).

5516 Background: The standard of treatment of stage I MOGCTs is surgery followed by BEP (bleomycin + etoposide + cisplatin) chemotherapy, except for stage IA dysgerminoma (D) and IAG1 immature teratoma (IT). Surveillance has emerged as a possible option to avoid adjuvant chemotherapy in IB-C1 D, IA-C G2 – G3 IT, and in stage IA mixed and yolk sac tumors (YST), after comprehensive surgical staging (CSS) with negative postoperative markers. The aim of this study was to analyze oncological outcome of stage I MOGCT patients included in the MITO9 study. Methods: MITO9 was a prospective observational study analyzing data collected between 2013 and 2018. 41 patients with stage I conservatively treated MOGCTs were included. Three groups were identified: group A. IA D and IAG1 IT candidate to surveillance according to guidelines; group B. stages IB-C1 D, stage IA-C G2-G3 IT, stage IA mixed and YST were consulted about the option of close surveillance vs adjuvant chemotherapy in case of CSS; group C. all other patients receiving BEP. Results: Median age was 25.6 years (range 14-40). Median follow up was 36,4 months. Group A included 12 patients, 5 IA G1 IT and 7 IA D. Group B included 24 patients. Of these, 2 out of 5 patients (40%) were positive at restaging and were excluded from surveillance protocol. Seven of the 22 remaining patients (31.8%) received chemotherapy, while 15 (68.1%) were enrolled in the surveillance protocol. Out of these 15 patients, 4 were stage IC D (one IC1, one IC2 and two IC3), 2 were mixed stage IA with YST tumor, 9 were G3 IT (four IA, three IC2, one IC3 and one IB). The 7 patients receiving chemotherapy were: 1 dysgerminoma IC2, 2 YST IA, 3 IT G3 (one IA and one IC2) and 1 mixed IA tumour. Group C included 5 patients, three IC YST and two mixed IC2 with YST. Survival of these patients was 100%, while disease free survival was 97.5%. Only one patient in C Group, a stage IA G3 IT treated with adjuvant BEP, relapsed as mature teratoma. None of the patients in the surveillance protocol experienced relapse. Conclusions: These data suggest that close surveillance could be an alternative option to avoid adjuvant chemotherapy in properly staged IB-C1 D, stage IA G2 – G3 IT, stage IA mixed and YST. These findings deserve further confirmation in an international cooperative setting.

Prognostic factors and oncological outcomes of ovarian yolk sac tumors: a retrospective multicentric analysis of 99 cases.

To investigate the clinico-pathological prognostic factors and treatment outcomes in patients with ovarian yolk sac tumors (YST). A multicenter, retrospective department database review was performed to identify patients with ovarian YST who underwent surgery between 2000 and 2017 at seven Gynecologic Oncology Centers in Turkey. The study group consisted of 99 consecutive patients with a mean age of 23.9years. While 52 patients had early stage (stage I-II) disease, the remaining 47 patients had advanced stage (stage III-IV) disease. Theuterus was preserved in 74 (74.8%) of the cases. The absence of gross residual disease following surgery was achieved in 76.8% of the cases. Of the 54 patients with lymph node dissection (LND), lymph node metastasis was detected in 10 (18.5%) patients. Of the 99 patients, only 3 patients did not receive adjuvant therapy, and most of the patients (91.9%) received BEP (bleomycin, etoposide, cisplatin) chemotherapy. Disease recurred in 21 (21.2%) patients. The 5-year disease-free survival (DFS) and overall survival (OS) in the entire cohort were 79.2% and 81.3%, respectively. In multivariate analysis, only residual disease following initial surgery was found to be significantly associated with DFS and OS in patients with ovarian YST (p = 0.026 and p = 0.001, respectively). Our results demonstrate the significance of achieving no visible residual disease in patients with ovarian YST. Fertility-sparing approach for patients with no visible residual disease affected neither DFS nor OS. Although high lymphatic involvement rate was detected, the benefit of LND could not be demonstrated.

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS539 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a complete response (CR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in achieving a CR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or Filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 11 sites open in UK (led by Cambridge Clinical Trials Unit), 19 sites open in the USA (led by Children’s Oncology Group). As of 23rd October 2018, 59 patients have been recruited. Clinical trial information: NCT02582697.

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS574 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in RR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days (D) 1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV (D 1, 8, 15 or D 2, 9, 16 of a 21 day cycle; D 1, 8 or D 2, 9 of a 14 day cycle); and peg G-CSF or Filgrastim; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 1/19 sites open in UK (led by Cambridge Clinical Trials Unit), 41 patients recruited by September 2017. International collaborations with USA (led by Children’s Oncology Group) and Ireland (led by Cancer Trials Ireland) confirmed with sites expected to open by late 2017 and more sites sought for stage 2. Clinical trial information: NCT02582697.

P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS4592 Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Accelerating regimens by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and paediatric age groups open to both males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open-label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in RRs and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 yrs with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT:Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF 6mg SC on Day 6; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30-day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 27 sites open in ANZ, 34 patients recruited by February 2017. International collaborations with UK (led by Cambridge Clinical Trials Unit) and US (led by Childrens Oncology Group) confirmed with sites expected to open by early 2017, and more sites sought for stage 2. Funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and previously CINSW. ANZCTR: ACTRN12613000496718. Clinical trial information: NCT02582697.

Sperm aneuploidy after testicular cancer treatment: data from a prospective multicenter study performed within the French Centre d’Étude et de Conservation des Oeufs et du Sperme network

To study sperm aneuploidy in a population of testicular cancer (TC) patients treated with the use of either bleomycin-etoposide-cisplatin (BEP) chemotherapy or radiotherapy. Multicenter prospective longitudinal study of TC patients analyzed before treatment and after 3, 6, 12, and 24months (T3-T24). Fifty-four TC patients and a control group of 10 fertile sperm donors. University hospital laboratories. Routine semen analyses; sperm aneuploidy and diploidy. Comparison of sperm characteristics and sperm chromosome abnormalities during TC patient follow-up. Semen characteristics recovered pretreatment values 12months after radiotherapy and 24months after more than two BEP cycles. A significant increase in sperm disomy YY and XX was observed in the TC group before treatment compared with the control group. After more than two BEP cycles, the mean sperm aneuploidy rate increased significantly at T12 and reached the pretreatment value at T24. After radiotherapy, the mean sperm aneuploidy returned to the pretreatment value at T12. At T24, nearly 40% of TC patients did not recover their pretreatment sperm aneuploidy rate. Genetic counseling of TC patients should include information on the potential elevated risk of aneuploid conceptus from sperm recovered after treatment and the necessity to postpone conception up to ≥12months after radiotherapy and ≥24months after more than two BEP chemotherapy cycles. However, few men receiving one or two BEP cycles and some dropouts are the main limitations of this study.

Accelerated BEP for metastatic germ cell tumors: Combined analysis of Australian and U.K. phase I/II trials.

4531 Background: Standard chemotherapy for advanced germ cell tumors is 3-weekly BEP (bleomycin, etoposide, cisplatin). 5-year overall survival is &gt; 90% in good risk disease, but only ~80% in intermediate and ~ 60% in poor risk disease. Accelerated versions of standard regimens have proven more effective in other malignancies. We aimed to determine tolerability and activity of accelerated (2-weekly) BEP by combining data from two single arm, multi-center, phase I/II trials. Methods: The UK trial (n=16) included patients with intermediate and poor risk metastatic germ cell tumours. The Australian trial (n=45) also included patients with radiologically measurable good risk disease. BEP chemotherapy was repeated every 2 weeks for 4 cycles (3 cycles for good risk). The Australian and UK regimens differed for cisplatin (20mg/m2 D1-5; 50mg/m2 D1-2), etoposide (100mg/m2 D1-5; 165mg/m2 D1-3), bleomycin (30kIU weekly x 12 or 9; 30kIU at 4-6 day intervals x 12), and pegylated G-CSF (6mg D6; 6mg D4) respectively. Primary endpoint for combined analysis was 2-year progression-free survival. Results: 61 patients were enrolled from 2004-09 (UK) and 2008-10 (Australia). 17 had poor risk, 28 intermediate risk, 16 good risk disease. Median follow-up is 27 months (range 6 to 81). Adverse events are presented in the table. 45 of 61 patients (74%) achieved a complete response to chemotherapy +/- surgery (9 of 17 poor risk (53%), 20 of 28 intermediate risk (71%), 16 of 16 good risk disease (100%)). 11 of 61 patients have relapsed. 2 patients have died of disease (both intermediate risk). 2 year overall survival is 98%. 2 year progression-free survival is 65% for poor risk, 86% for intermediate risk, and 92% for good risk disease. Conclusions: Efficacy data are promising, particularly for intermediate and poor risk disease. Adverse events appear comparable to standard BEP. These results provide the rationale for an international trial randomised trial comparing accelerated and standard versions of BEP. [Table: see text]

Surgical staging and adjuvant chemotherapy in the management of patients with adult granulosa cell tumors of the ovary

ObjectiveTo analyze the role of surgical staging and adjuvant chemotherapy in patients with adult type granulosa cell tumor (GCT) of the ovary. MethodsPatients were divided into those with early-stage (stages I–II, n=93) and advanced-stage (stages III–IV, n=13) GCT and analyzed separately in this retrospective study. ResultsOf the 93 patients with early-stage GCT, 30 were completely staged and 25 underwent lymph node dissection. After surgery, 17 patients received adjuvant chemotherapy with bleomycin/etoposide/cisplatin (BEP). None had lymph node metastasis. Completely staged patients had no recurrence or deaths. However, recurrences were observed in 9 of 63 patients (14.3%) who did not undergo complete staging, with four (6.3%) dying due to disease. The 5-year disease-free survival (DFS) rates of groups with and without complete staging were 100% and 84%, respectively (P=0.037). Adjuvant chemotherapy was not significantly associated with DFS (P=0.193). All patients with advanced-stage GCT underwent optimal cytoreduction and received adjuvant chemotherapy with BEP. None of the 6 patients who completed 6 cycles of BEP had recurrence, whereas 5 of the 7 patients (71.4%) who received fewer than 6 cycles of BEP had recurrences and 3 (42.9%) died due to disease. The 5-year DFS rates of these two groups were 100% and 50%, respectively (P=0.022), with cycles of chemotherapy being the only significant factor for DFS in patients with advanced-stage GCT. ConclusionsComplete surgical staging is recommended, but lymph node removal is not recommended for early-stage GCT. Optimal debulking followed by six cycles of BEP chemotherapy is recommended for advanced-stage GCT.

SEOM guidelines: non-seminomatous germ cell cancer (NSGCC)

Non-seminomatous germ cell cancer (NSGCC) is a curable disease; its treatment has not essentially changed since the 1980s. BEP (bleomycin, etoposide, cisplatin) chemotherapy remains the standard of care. NSGCC's management can be summarised by three trees of decision, which contemplate staging, treatment with chemotherapy and management of postchemotherapy residual disease. The role of high-dose chemotherapy remains to be established. TIP (paclitaxel, iposfamide, cisplatin) chemotherapy is still the standard salvage treatment for patients progressing after BEP chemotherapy. Surgical removal of any residual disease is mandatory. For patients with poor prognosis, consultation with a centre of expertise is strongly recommended.

Outcomes after bleomycin, etoposide and cisplatin combination chemotherapy in patients with ovarian yolk sac tumor

Objective: The aim of this study was to evaluate the oncologic and reproductive outcomes of patients with ovarian yolk sac tumor after bleomycin, etoposide, cisplatin (BEP) chemotherapy following surgery. Methods: Of 145 patients with histologically confirmed malignant ovarian germ cell tumor, 43 had yolk sac tumor and received BEP chemotherapy after surgery. A retrospective analysis of these patients was performed. Results: The mean age of 43 patients was 24.8 years (range, 7 to 59 years). Thirty eight patients were iparous. Of 179 BEP chemotherapy cycles, grade 1~2 hematologic and non-hematologic adverse events occurred in 46 cycles in 21 patients. Thirty nine patients showed complete remission, 1 patient showed partial remission, and 3 patient had progressive disease during BEP chemotherapy. After median follow-up time of 57 months (range, 3 to 153 months), 5 patients had recurrent disease and three of them died of disease. The 5-year recurrence free survival rate and overall survival rate were 86% and 94%, respectively. After chemotherapy, all but one premenarchal patients had normal menstruation. Of them 5 patients tried to conceive and 3 of them succeeded in pregnancy. Conclusion: BEP chemotherapy was very safe and effective in patients with ovarian yolk sac tumor. Survival outcomes are excellent and reproductive outcomes are promising after BEP chemotherapy.

Yolk sac tumours of the ovary: Evaluation of clinicopathological features and prognostic factors

Objective To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST). Study design We reviewed the medical records of 32 women with ovarian YST treated from 1990 to 2006 at two centres. Results The median follow-up was 36 months. The median age was 22 (range, 9–68). Two patients were postmenopausal. The most common symptoms at diagnosis included abdominal swelling or mass (72%) and abdominopelvic pain (62%). The location of the tumour was bilateral in 2 cases. Eight patients were in stage I, 4 patients in stage II, 17 patients in stage III, and 3 patients in stage IV. Eighteen patients underwent unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two cystectomy, while 10 patients had total abdominal hysterectomy and two bilateral salpingo-oophorectomy. Of 32 patients who received postoperative chemotherapy, 27 were treated with a bleomycin/etoposide/cisplatin (BEP) regimen. Seventy-two percent of patients were alive at the last follow-up visit. Ten (31%) patients suffered from a recurrence of the disease with a median time to recurrence of 8 months (range, 6–28 months). The most common site of recurrence was the intra-abdominal space, with 8 patients. Only one patient who had recurrence could be salvaged. Fertility-sparing surgery was found at least as effective as radical surgery. While age, histology (mixed vs. pure), stage, tumour size, ascites, and marker levels were not found as prognostic factors, the presence of residual tumour ( P = 0.014) and BEP chemotherapy ( P = 0.016) were significant prognostic factors in univariate analysis. Conclusions In patients with ovarian YST, fertility-sparing surgery is as effective as radical surgery. Optimal cytoreductive surgery and standard BEP regimen are the most decisive prognostic factors. In these tumours, adjunctive therapeutic modalities to eradicate intra-abdominal disease and effective salvage therapy strategies are needed.

Survival and reproductive function of 52 women treated with surgery and bleomycin, etoposide, cisplatin (BEP) chemotherapy for ovarian yolk sac tumor

BackgroundOvarian yolk sac tumor (YST) is a very rare malignancy arising in young women. Chemotherapy has dramatically improved the prognosis. Current treatment consists of surgery followed by bleomycin, etoposide, and cisplatin (BEP) chemotherapy. However, given the rarity of this tumor, ovarian YST-specific survival and outcome after such treatment are not precisely known. Patients and methodsThis report concerns prospectively recorded cases that were either treated at Institut Gustave Roussy (Villejuif, France) or referred there for advice about therapy. From 1990 to 2006, 52 patients underwent surgery followed by BEP chemotherapy. Data on patient characteristics, treatment, survival, and fertility outcome were analyzed to assess treatment efficacy and gonadal toxicity after achieving a complete remission. ResultsThirty-five patients had stage I/II tumors while 17 patients presented with stage III/IV disease. With a median follow-up of 68 months, the overall 5-year survival and disease-free survival rates were 94% and 90%, respectively. Forty-one women underwent fertility-sparing surgery. Pregnancy was achieved in 12 of 16 (75%) women who attempted conception. Overall, 19 pregnancies have been recorded. ConclusionsBEP chemotherapy following fertility-sparing surgery is a very effective treatment of ovarian YSTs. Most of the patients who attempt conception after complete remission will have children.

Curing metastatic testicular cancer.

Our initial studies with cisplatin + vinblastine + bleomycin began 27 years ago in 1974, changing the cure rate for disseminated disease from 5 to 60%. Subsequently, through random prospective clinical trials, we have modified the treatment regimen to reduce both the duration and dosages of the chemotherapy drugs. Cisplatin + etoposide was first used at Indiana University as salvage chemotherapy in 1978, representing the first time that a solid tumor had been cured with second-line chemotherapy. We next did a clinical trial comparing bleomycin + etoposide + cisplatin (BEP) to cisplatin + vinblastine + bleomycin. The BEP regimen was proven to have less toxicity and a higher cure rate and therefore, since 1984, has been standard chemotherapy. More recent studies have evaluated the use of lesser chemotherapy to maintain the same cure rate for patients with good-prognosis disease. Standard therapy for these patients is either three courses of BEP or four courses of EP, and over 90% of these patients will be cured of their disease. Patients who are not cured with their initial BEP chemotherapy are usually treated with salvage chemotherapy. Approximately 50% of these testicular cancer patients will subsequently be cured with salvage chemotherapy with tandem transplant of high-dose chemotherapy with peripheral stem cell rescue. Testicular cancer has become a model for a curable neoplasm. In the early 1970s, metastatic testicular cancer was associated with only 5% survival. Today, with modern chemotherapy and surgery techniques, 80% of patients will survive their disease.

Late Recurrence in Ovarian Dysgerminoma with Successful Response to Standard Adjuvant Chemotherapy: A Case Report and Review of the Literature

Background. Ovarian dysgerminomas are quite amenable to treatment and very good cure rates are achieved even with advanced disease. However, recent literature suggests that late recurrence may be associated with a poorer prognosis and bleomycin/etoposide/cisplatin (BEP) chemotherapy may play only a limited role in its management. We present a patient who had a late recurrence of ovarian dysgerminoma with successful treatment outcome.Case. A 25-year-old woman was diagnosed with a stage IC ovarian dysgerminoma in 1983 and did not undergo adjuvant treatment. She had late recurrence 12 years later with good treatment response to BEP chemotherapy given in a semiadjuvant fashion.Conclusion. Our case demonstrates that BEP chemotherapy still plays an important role in treatment of late recurrence in ovarian dysgerminomas provided there is small volume disease at time of detection. Also important is long-term surveillance in an effort to detect recurrence while still small in volume and potentially curable.

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

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. 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. 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. 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.

Primary Endodermal Sinus Tumor of the Omentum

Endodermal sinus tumor (EST) is a rare neoplasm which usually arises in the testis or ovary. But extragonadal EST is well recognized and may arise in a wide array of sites such as the mediastinum, vagina, and brain. We report a case of primary EST of the omentum and to our knowledge it is the first case of omental EST in the literature. A 45-year-old woman with a history of abdominal distension was treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy, followed by four cycles of BEP (bleomycin, etoposide, cisplatin) combination chemotherapy. Microscopically, the tumor exhibited typical patterns of EST and stained for α-fetoprotein and cytokeratin. She has remained free of disease for 10 months of follow-up. According to previous studies, debulking surgery and BEP chemotherapy were used as primary therapy with good results. The subject of extragonadal EST is reviewed, and the possible histogenesis of this tumor at such a rare site is discussed.