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European Urology Mar 2015Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required.
OBJECTIVE
To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial.
DESIGN, SETTING, AND PARTICIPANTS
We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres.
INTERVENTION
BEP (bleomycin 30,000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15,000 IU).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates.
RESULTS AND LIMITATIONS
A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS.
CONCLUSIONS
The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial.
PATIENT SUMMARY
In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration.
TRIAL REGISTRATION
ISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Disease Progression; Disease-Free Survival; Etoposide; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Proportional Hazards Models; Testicular Neoplasms; Time Factors; Treatment Outcome; United Kingdom; Vincristine; Young Adult
PubMed: 25001888
DOI: 10.1016/j.eururo.2014.06.034 -
British Journal of Cancer Sep 2011We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim...
BACKGROUND
We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability.
METHODS
Sixteen male patients with intermediate or poor prognosis metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day cycle for a planned relative dose-density of 1.5 compared with standard BEP.
RESULTS
Eleven intermediate and five poor prognosis patients were treated. In all, 14 of 16 patients completed the study treatment. Toxicities were comparable to previous studies using standard BEP, except for mucositis and haematological toxicity that were more severe. The overall relative dose-density for all 16 patients was mean 1.38 (range 0.72-1.5; median 1.46). Complete response was achieved after chemotherapy alone in two patients (13%) and following chemotherapy plus surgery in nine additional patients (56%). Four patients (25%) had a partial response and normalised their marker levels. At a median follow-up of 4.4 years (range 2.1-6.8) the estimated 5-year progression-free survival probability is 81% (95% CI 64-100%).
CONCLUSION
Accelerated BEP is tolerable without major additional toxicity. A randomised controlled trial will be required to obtain comparative efficacy data.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Etoposide; Filgrastim; Granulocyte Colony-Stimulating Factor; Hearing Loss; Humans; Lung Diseases; Male; Neoplasms, Germ Cell and Embryonal; Polyethylene Glycols; Prognosis; Recombinant Proteins
PubMed: 21847130
DOI: 10.1038/bjc.2011.309 -
European Journal of Cancer (Oxford,... Mar 2020Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term outcomes with intensive induction chemotherapy (carboplatin, bleomycin, vincristine and cisplatin/bleomycin, etoposide and cisplatin) and standard bleomycin, etoposide and cisplatin in poor prognosis germ cell tumours: A randomised phase II trial (ISRCTN53643604).
BACKGROUND
Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, vincristine and cisplatin/BEP), met response targets in a randomised, phase II trial (74% complete response or partial response marker negative, 90% confidence interval (CI) 61%-85%).
AIM
To assess long-term outcomes and late toxicity associated with CBOP/BEP.
METHODS
Patients with poor prognosis extracranial GCT were randomised to 4xBEP or CBOP/BEP (2xCBOP, 2xBO, 3xBEP with 15,000iu of bleomycin). Low-dose, stabilising chemotherapy before entry was permitted. Response rates (primary outcome) were reported previously. Here, we report secondary outcomes: progression-free survival (PFS), overall survival (OS) and late toxicity. Prognostic factors and the impact of marker decline are assessed in exploratory analysis.
RESULTS
Eighty-nine patients (43 CBOP/BEP) were randomised. After median 63 months follow-up, 3-year PFS is 55.7% (95% CI: 39.7%, 69.0%) for CBOP/BEP and 38.7% (95% CI: 24.7%, 52.4%) for BEP (hazard ratio [HR]: 0.59 (0.33, 1.06), p = 0.079). Three-year OS is 65.0% (48.8%, 77.2%) and 58.5% (43.0%, 71.2%), respectively (HR: 0.79 (0.41, 1.52), p = 0.49). Twelve-month toxicity was affected by subsequent treatments, with no clear differences between arms. Stabilising chemotherapy was associated with poorer PFS (HR: 2.09 (1.14, 3.81), p = 0.017), whereas unfavourable marker decline, in 60 (70%) patients, was not.
CONCLUSION
Although not powered for PFS, results for CBOP/BEP are promising. Impact on OS was less clear (and will be affected by subsequent therapy). Further study in an international phase III trial is warranted.
TRIAL REGISTRATION
ISRCTN 53643604.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Etoposide; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Germ Cell and Embryonal; Prognosis; Survival Rate; Vincristine; Young Adult
PubMed: 32007714
DOI: 10.1016/j.ejca.2019.12.028 -
Journal of Clinical Oncology : Official... Mar 2012To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in... (Comparative Study)
Comparative Study Randomized Controlled Trial
Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983.
PURPOSE
To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).
PATIENTS AND METHODS
Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m(2) in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual.
RESULTS
Accrual was from November 1998 to April 2009. A total of 169 patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different.
CONCLUSION
T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.
Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Disease-Free Survival; Etoposide; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Paclitaxel; Treatment Outcome
PubMed: 22271474
DOI: 10.1200/JCO.2011.37.0171 -
Medicine Jul 2022Ovarian yolk sac tumor (YST) is a very rare malignant tumor in young women. This study aimed to explore the clinicopathological prognostic characteristics and... (Review)
Review
Clinicopathological features, prognosis, and fertility outcomes in Chinese Han women treated for ovarian yolk sac tumor: A retrospective case series study from two tertiary-care academic medical centers.
OBJECTIVE
Ovarian yolk sac tumor (YST) is a very rare malignant tumor in young women. This study aimed to explore the clinicopathological prognostic characteristics and reproductive outcomes of Chinese Han patients.
METHODS
To describe a case series study, we reviewed the clinicopathological data of 50 YST patients treated from 2 tertiary medical academic medical centers from January 2009 to December 2019. The Akaike information criterion was used to select variables. The influence of relevant characteristics on prognosis factors was analyzed by the Cox proportional hazard model.
RESULTS
The median follow-up time was 64.5 months (range from 3 to 124 months). The median age was 22.7 years (3 to 34 years). Abdominal pain (54.0%) or mass (42.0%) were the most common clinical symptoms in the early stage of diagnosis. The tumors were located bilaterally in 4 cases. 27 patients, 7 patients, 13 patients, and 3 patients were in stage I, II, III, and IV, respectively. Twenty-one stage I patients and 12 stage II to IV patients underwent fertility-preserving surgery. Of the 50 patients who received postoperative chemotherapy, 49 received the BEP regimen. At the last follow-up, 92% of the patients were still alive. The overall survival rate and disease-free survival rate were 91.6% and 90.6%, respectively. Recurrence occurred in 7 (14%) patients with a median survival time of 16.7 months (range from 3 to 50 months). Six patients had recurrence in the abdominal space. The percentage of Ki67 (P = .01) and tumor size (P = .03) were 2 important prognostic factors in multivariate analysis. In terms of survival outcomes, fertility-preserving surgery can be equivalent to radical surgery. Sixteen patients tried to conceive, and 6 patients with advanced-stage succeeded in 10 pregnancies. Of these, 6 patients successfully gave birth to 6 healthy babies.
CONCLUSIONS
The diagnosis of YST of childbearing age is very rare. Because the failure of primary treatment is related to the residual disease after salvage surgery, the fertility and survival results of patients undergoing fertility-preserving surgery are promising.
Topics: Academic Medical Centers; Adult; China; Endodermal Sinus Tumor; Female; Fertility; Humans; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pregnancy; Prognosis; Retrospective Studies; Young Adult
PubMed: 35866762
DOI: 10.1097/MD.0000000000029868 -
Cancer Science Jan 2010Today, approximately 80% of men with metastatic testicular cancer can be cured with chemotherapy combined with the appropriate surgery. The improved treatment outcome... (Review)
Review
Today, approximately 80% of men with metastatic testicular cancer can be cured with chemotherapy combined with the appropriate surgery. The improved treatment outcome has led to the stratification of patients with metastatic disease by the consensus prognostic index; the International Germ Cell Cancer Consensus Group classification. Currently, the first-line chemotherapy with bleomycin, etoposide, and cisplatin (BEP) remains the standard management of metastatic testicular cancer. Three cycles of BEP for good-prognosis patients and four cycles of BEP for intermediate- and poor-prognosis patients are the standard first-line chemotherapy. To achieve the optimal outcome, BEP should be given with appropriate supportive care and risk assessment for toxicity. Although no universal prognostic criteria have been defined for the recurrent or refractory disease, the risk-adapted approach may clarify the role of ifosfamide- and paclitaxel-containing conventional-dose chemotherapy or high-dose chemotherapy in the second-line setting. Several investigators reported recent improvement of treatment outcome of testicular cancer patients, especially those with poor prognosis. Along with the progress in chemotherapy, the risk-adapted management at experienced hospitals seems to be responsible for the recent progress in treatment outcome.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Etoposide; Humans; Male; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal; Randomized Controlled Trials as Topic; Risk; Risk Assessment; Salvage Therapy; Testicular Neoplasms
PubMed: 19922501
DOI: 10.1111/j.1349-7006.2009.01373.x -
PLoS Medicine Feb 2022Malnutrition among women of childbearing age is especially prevalent in Asia and sub-Saharan Africa and can be harmful to the fetus during pregnancy. In the most... (Comparative Study)
Comparative Study
Cost-effectiveness of antenatal multiple micronutrients and balanced energy protein supplementation compared to iron and folic acid supplementation in India, Pakistan, Mali, and Tanzania: A dynamic microsimulation study.
BACKGROUND
Malnutrition among women of childbearing age is especially prevalent in Asia and sub-Saharan Africa and can be harmful to the fetus during pregnancy. In the most recently available Demographic and Health Survey (DHS), approximately 10% to 20% of pregnant women in India, Pakistan, Mali, and Tanzania were undernourished (body mass index [BMI] <18.5 kg/m2), and according to the Global Burden of Disease (GBD) 2017 study, approximately 20% of babies were born with low birth weight (LBW; <2,500 g) in India, Pakistan, and Mali and 8% in Tanzania. Supplementing pregnant women with micro and macronutrients during the antenatal period can improve birth outcomes. Recently, the World Health Organization (WHO) recommended antenatal multiple micronutrient supplementation (MMS) that includes iron and folic acid (IFA) in the context of rigorous research. Additionally, WHO recommends balanced energy protein (BEP) for undernourished populations. However, few studies have compared the cost-effectiveness of different supplementation regimens. We compared the cost-effectiveness of MMS and BEP with IFA to quantify their benefits in 4 countries with considerable prevalence of maternal undernutrition.
METHODS AND FINDINGS
Using nationally representative estimates from the 2017 GBD study, we conducted an individual-based dynamic microsimulation of population cohorts from birth to 2 years of age in India, Pakistan, Mali, and Tanzania. We modeled the effect of maternal nutritional supplementation on infant birth weight, stunting and wasting using effect sizes from Cochrane systematic reviews and published literature. We used a payer's perspective and obtained costs of supplementation per pregnancy from the published literature. We compared disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs) in a baseline scenario with existing antenatal IFA coverage with scenarios where 90% of antenatal care (ANC) attendees receive either universal MMS, universal BEP, or MMS + targeted BEP (women with prepregnancy BMI <18.5 kg/m2 receive BEP containing MMS while women with BMI ≥18.5 kg/m2 receive MMS). We obtained 95% uncertainty intervals (UIs) for all outputs to represent parameter and stochastic uncertainty across 100 iterations of model runs. ICERs for all scenarios were lowest in Pakistan and greatest in Tanzania, in line with the baseline trend in prevalence of and attributable burden to LBW. MMS + targeted BEP averts more DALYs than universal MMS alone while remaining cost-effective. ICERs for universal MMS compared to baseline IFA were $52 (95% UI: $28 to $78) for Pakistan, $72 (95% UI: $37 to $118) for Mali, $70 (95% UI: $43 to $104) for India, and $253 (95% UI: $112 to $481) for Tanzania. ICERs for MMS + targeted BEP compared to baseline IFA were $54 (95% UI: $32 to $77) for Pakistan, $73 (95% UI: $40 to $104) for Mali, $83 (95% UI: $58 to $111) for India, and $245 (95% UI: $127 to $405) for Tanzania. Study limitations include generalizing experimental findings from the literature to our populations of interest and using population-level input parameters that may not reflect the heterogeneity of subpopulations. Additionally, our microsimulation fuses multiple sources of data and may be limited by data quality and availability.
CONCLUSIONS
In this study, we observed that MMS + targeted BEP averts more DALYs and remains cost-effective compared to universal MMS. As countries consider using MMS in alignment with recent WHO guidelines, offering targeted BEP is a cost-effective strategy that can be considered concurrently to maximize benefits and synergize program implementation.
Topics: Adolescent; Adult; Cohort Studies; Cost-Benefit Analysis; Dietary Proteins; Dietary Supplements; Disability-Adjusted Life Years; Energy Intake; Female; Folic Acid; Humans; India; Infant, Newborn; Iron; Male; Mali; Micronutrients; Middle Aged; Pakistan; Pregnancy; Prenatal Care; Tanzania; Young Adult
PubMed: 35192606
DOI: 10.1371/journal.pmed.1003902 -
British Journal of Cancer Jun 1995We have investigated whether an alternating induction chemotherapy regimen of PVB/BEP is superior to BEP in patients with poor-prognosis testicular non-seminoma. A total... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Four cycles of BEP versus an alternating regime of PVB and BEP in patients with poor-prognosis metastatic testicular non-seminoma; a randomised study of the EORTC Genitourinary Tract Cancer Cooperative Group.
We have investigated whether an alternating induction chemotherapy regimen of PVB/BEP is superior to BEP in patients with poor-prognosis testicular non-seminoma. A total of 234 eligible patients were randomised to receive an alternating schedule of PVB/BEP for a total of four cycles or four cycles of BEP. Poor prognosis was defined as any of the following: lymph node metastases larger than 5 cm, lung metastases more than four in number or larger than 2 cm, haematogenic spread outside the lungs, such as in liver and bone, human chorionic gonadotrophin > 10,000 IU l-1 or alphafetoprotein > 1000 IU l-1. The complete response (CR) rates to PVB/BEP and BEP were similar, 76% and 72% respectively (P = 0.58). In addition, there was no significant difference in relapse rate, disease-free and overall survival at an average follow-up of 6 years. The 5-year progression-free and survival rates in both treatment groups were approximately 80%. The PVB/BEP regime was more toxic with regard to bone marrow function; the frequencies of leucocytes below 1000 microliters-1, leucocytopenic fever and platelets below 25,000 microliters-1, throughout four cycles were 28% vs 5% (P < 0.001), 16% vs 5% (P = 0.006), and 10% vs 1% (P = 0.001) respectively. Neuropathy also occurred more often in the PVB/BEP arm: 47% vs 25% (P = 0.001). This study shows that an alternating regimen of PVB/BEP is not superior to BEP and that it is more myelo- and neurotoxic.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Neoplasms; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Etoposide; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Prognosis; Survival Rate; Testicular Neoplasms; Time Factors; Vinblastine
PubMed: 7540039
DOI: 10.1038/bjc.1995.254 -
Journal of Cancer Research and... 2021Bleomycin, etoposide, and cisplatin (BEP) regimen is the standard treatment for germ-cell tumors (GCTs). Bleomycin-induced pulmonary toxicity (BPT) is fatal and...
AIM
Bleomycin, etoposide, and cisplatin (BEP) regimen is the standard treatment for germ-cell tumors (GCTs). Bleomycin-induced pulmonary toxicity (BPT) is fatal and dose-limiting toxicity associated with this regimen. In this study, we aimed to identify the frequency and risk factors of BPT in South Indian GCT patients receiving BEP regimen.
PATIENTS AND METHODS
The study was carried out in the Department of Medical Oncology, Regional Cancer Centre at a tertiary care hospital in South India. All the patients with GCT (testicular and ovarian) who were receiving BEP regimen from December 2014 to May 2018 were included in the study. BPT was defined as the presence of radiological features and/or clinical symptoms during or post-treatment.
RESULTS
BPT was observed in 11 (27%) patients of 41 analyzed patients. Five (12%) patients developed BPT during treatment whereas six (15%) patients developed BPT post-treatment. Cumulative bleomycin dose ≥240 mg (relative risk 3.8, confidence interval: 1.2-12.2,P =0.02) was found to increase the risk of BPT. Three-year overall survival in patients with and without toxicity was 82% and 93%, respectively.
CONCLUSIONS
The frequency of BPT in the study population is 27%, and cumulative bleomycin dose ≥240 mg has been found to be associated with increased risk of developing BPT. BPT does not negatively impact survival outcome in GCT patients receiving BEP regimen.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Etoposide; Female; Follow-Up Studies; Humans; Incidence; India; Lung; Lung Diseases; Male; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Risk Factors; Survival Analysis; Testicular Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; Young Adult
PubMed: 34121690
DOI: 10.4103/jcrt.JCRT_348_19 -
Dermatology Online Journal Dec 2013A 21-year-old woman presented with a pruritic eruption on her trunk and extremities after receiving bleomycin for treatment of stage III ovarian germ-cell tumor....
A 21-year-old woman presented with a pruritic eruption on her trunk and extremities after receiving bleomycin for treatment of stage III ovarian germ-cell tumor. Physical examination was consistent with bleomycin-induced flagellate erythema. We discuss the pathophysiologic mechanism that produces this dermatitis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Drug Eruptions; Erythema; Etoposide; Female; Humans; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Young Adult
PubMed: 24365007
DOI: No ID Found