Outcome of children with malignant germ cell tumors by response status at the end of induction chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10023-10023
Author(s):  
Adriana Fonseca ◽  
Doojduen Villaluna ◽  
Mark D. Krailo ◽  
A. Lindsay Frazier ◽  
Furqan Shaikh
Keyword(s):  
Germ Cell ◽  
Induction Chemotherapy ◽  
Small Sample Size ◽  
Germ Cell Tumors ◽  
Response Assessment ◽  
Complete Response ◽  
Small Sample ◽  
Phase Iii ◽  
Salvage Regimen ◽  
Malignant Germ Cell Tumors

10023 Background: The management of pediatric malignant germ cell tumors (MGCTs) includes induction therapy with 3-4 cycles cisplatin, etoposide, bleomycin (PEb). The current practice recommends 2-3 cycles of PEb (total 6 cycles) as consolidation therapy if response is not complete at the end of induction, a significantly different approach than that used in adult patients who receive a standard number of cycles. Furthermore, there is no evidence supporting the addition of a consolidation phase with PEb in pediatric patients with MGCTs. Methods: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs (AGCT0132). All patients received 3 cycles of PEb and underwent response assessment at the end of induction. Complete Response (CR) was defined as negative tumor markers and no viable residual lesion. Patients in CR were not to receive any further chemotherapy. Patients not in CR were prescribed 3 additional cycles of PEb as consolidation. Event-free survival (EFS) and Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Among 210 patients enrolled, 193 patients had CR after 3 cycles of induction chemotherapy, and their post-induction 4yr-EFS and OS was 93% and 99%. Fifteen patients were not in CR at the end of the first 3 cycles and received additional chemotherapy, and their 4yr-EFS and OS was 51% and 60%. Conclusions: Children with MGCTs who have a partial response after the first 3 cycles of chemotherapy had an inferior outcome compared to those with a CR, despite receiving additional cycles of PEb chemotherapy. Thus, we conclude that consolidation is of unclear benefit. Although our results are limited by small sample size and lack of comparator, we propose that pediatric MGCT patients who fail to achieve a CR after standard induction chemotherapy should receive a salvage regimen with different agents rather than consolidation with more cycles of the same chemotherapy.

Intensive Induction Chemotherapy With CBOP/BEP in Patients With Poor Prognosis Germ Cell Tumors

2003 ◽  
Vol 21 (5) ◽  
pp. 871-877 ◽  
Author(s):  
J.A. Christian ◽  
R.A. Huddart ◽  
A. Norman ◽  
M. Mason ◽  
S. Fossa ◽  
...  
Keyword(s):  
Germ Cell ◽  
Induction Chemotherapy ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
Phase Iii ◽  
Royal Marsden Hospital ◽  
Prognosis Group ◽  
Male Patients ◽  
Patients With Poor Prognosis

Purpose: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. Patients and Methods: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. Results: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P = .24). Conclusion: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.

Early progression (progr) in patients (pts) with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation (gBRCAm): Phase III POLO trial of olaparib (O) versus placebo (P).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 750-750
Author(s):  
Teresa Macarulla ◽  
Hedy L. Kindler ◽  
Pascal Hammel ◽  
Michele Reni ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Brca Mutation ◽  
Standard Of Care ◽  
Complete Response ◽  
Small Sample ◽  
Phase Iii ◽  
Stepwise Logistic Regression ◽  
Continuous Variables ◽  
Platinum Based Chemotherapy ◽  
Stepwise Logistic Regression Model

750 Background: In POLO (NCT02184195), maintenance O was associated with significant progr-free survival benefit vs P in pts with a gBRCAm and mPaC (Golan NEJM 2019). Early progr or death (within 4 months [m]) occurs in ~35−45% of pts on standard-of-care first-line (1L) chemotherapy for mPaC (Conroy NEJM 2011; von Hoff NEJM 2013); however, predictive factors are currently unknown and early progr has not been addressed in the maintenance setting. We examined factors potentially associated with early progr in POLO. Methods: Following ≥16 weeks of 1L platinum-based chemotherapy (PBC) without progr, pts were randomized to maintenance O (tablets; 300 mg bd) or P until progr or unacceptable toxicity. Early progr was defined as progr (by blinded independent central review) or death within 4 m of randomization. A stepwise logistic regression model included baseline (BL) factors age, albumin, lactate dehydrogenase (LDH), global health status (GHS) and physical functioning (PhysF) as continuous variables, and discrete variables listed in the Table. Results: 62/154 randomized pts (40%) were defined as early progressors (EP; Table). Due to missing BL data, the multivariate analysis included 127 pts (56 EPs [44%]). Lower BL PhysF score (continuous) was significantly associated with early progr ( P= 0.02); no difference for partial/complete response (PR/CR) vs stable disease (SD). Conclusions: While small sample size limited analysis power, PhysF score was the only BL factor significantly associated with early progr in pts with a gBRCAm and mPaC in the POLO trial of maintenance O vs P. Clinical trial information: NCT02184195 . [Table: see text]

Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study.

1993 ◽  
Vol 11 (4) ◽  
pp. 598-606 ◽  
Author(s):  
D F Bajorin ◽  
M F Sarosdy ◽  
D G Pfister ◽  
M Mazumdar ◽  
R J Motzer ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Complete Response ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Free Survival ◽  
To Receive ◽  
Carboplatin Dose ◽  
Good Risk

PURPOSE This multicenter, randomized phase III clinical trial evaluated the efficacy of etoposide plus carboplatin (EC) versus etoposide plus cisplatin (EP) in good-risk germ cell tumor (GCT) patients. PATIENTS AND METHODS Between October 1986 and December 1990, 270 patients with good-risk GCTs were randomized to receive four cycles of either EP or EC. The etoposide dose in all patients was 100 mg/m2 on days 1 through 5. EP patients received cisplatin at 20 mg/m2 on days 1 through 5 and therapy was recycled at 21-day intervals. For EC patients, the carboplatin dose was 500 mg/m2 on day 1 of each cycle and the EC recycling interval was 28 days. RESULTS Two hundred sixty-five patients were assessable: 131 patients treated with EC and 134 treated with EP. One hundred fifteen of 131 assessable patients (88%) treated with EC achieved a complete response (CR) versus 121 of 134 patients (90%) treated with EP (P = .32). Sixteen patients (12%) treated with EC relapsed from CR versus four patients (3%) treated with EP. Therefore, 32 patients (24%) who received carboplatin experienced an event (incomplete response [IR] or relapse) compared with 17 of 134 patients (13%) who received cisplatin (P = .02). At a median follow-up of 22.4 months, event-free and relapse-free survival were inferior for patients treated with EC (P = .02 and P = .005, respectively). No difference in overall survival was evident (P = .52). CONCLUSION Two-drug therapy with EC using this dose and schedule was inferior to therapy with EP. Cisplatin remains as the standard platinum analog in the treatment of patients with good-risk GCTs. Carboplatin should be restricted to investigational trials in GCT.

scholarly journals Metastatic germ cell tumor with complete response-7 years follow up

2017 ◽  
Vol 5 (12) ◽  
pp. 5443
Author(s):  
Branislava Golub Jakovljevic ◽  
Dejan Đokanović ◽  
Snježana Miličević ◽  
Anđa Škobić ◽  
Dejan Ćazić ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Complete Response ◽  
Cell Tumor ◽  
Uncommon Disease ◽  
Malignant Germ Cell Tumors ◽  
Sites Of Metastases ◽  
Very High

Cancer of the testis is a relatively uncommon disease, accounting for approximately 1-1.5% of all cancers in males.  5% of the malignant germ cell tumors are made of extragonadal origin. Germ cell tumors occur in men younger, usually between 20 and 35 years old. We report a case of a patient with metastatic extragonadal germ cell tumor with multiple sites of metastases, and very high initial values of tumor marker human chorionic gonadotrophin (HCG)- 1351308. At the time of diagnosis, the patient was in a very poor general condition. After the applied chemotherapy, there was a complete response and 7 years later the patient is without any symptoms of disease.

Endoglin (CD105) expression in non-seminomatous germ cell tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16036-e16036 ◽  
Author(s):  
Swati Sikaria ◽  
Shefali Chopra ◽  
Shigang Xiong ◽  
Dongyun Yang ◽  
Charles P. Theuer ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Cells ◽  
Internal Control ◽  
Small Sample Size ◽  
Germ Cell Tumors ◽  
Tumor Vasculature ◽  
Small Sample ◽  
Positive Staining ◽  
Refractory Disease ◽  
Potential Target

e16036 Background: Nonseminomatous germ cell tumors are known for hematogenous spread and new therapeutics are needed. Endoglin (CD105) is a cell-surface protein that is overexpressed on endothelial cells and a potential target for anti-angiogenic therapy. Preclinical studies demonstrate overexpression of CD105 in tumor vasculature and targeting CD105 in murine models have resulted in tumor regression. We examine CD105 expression in tumor cells and tumor vasculature of patients with non-seminomatous germ cell tumor. Methods: Slides of NSGCT were incubated with rabbit anti-human CD105 followed by horseradish peroxidase-labeled anti-rabbit IgG and then with substrate chromogen followed by hematoxylin counterstaining. Human kidney served as positive internal control. Endoglin positivity was assessed in tumor cells and vasculature and graded (0-3+). Results: 37 total samples were obtained, 4 were excluded (3 seminoma, 1 pure teratoma) All 37 specimens had positive endoglin staining in tumor vasculature. Of 33 specimens, 79% (26/33) had positive staining for endgolin, whereas 21% did not (7/33). (Table 1)Of patients with relapsed or refractory disease, 83% (5/6) stained positively for CD105. While this is a small sample size, 3+ staining was seen in 50% of patients (n=6) with relapsed or refractory disease, but vs 18.5% of patients (n=27) in 1stremission (Fisher’s exact test p =0.14). Conclusions: Endoglin was highly expressed in tumor and tumor vasculature of NSGCT. This small pilot study suggests high (>50%) expression correlating with relapsed or refractory disease. Further samples from patients with relapsed or refractory disease are being collected and analyzed. Endoglin is a potential target for study in non-seminomatous germ cell tumors. [Table: see text]

Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors

2003 ◽  
Vol 99 (1) ◽  
pp. 106-114 ◽  
Author(s):  
Masato Kochi ◽  
Youichi Itoyama ◽  
Shoji Shiraishi ◽  
Isao Kitamura ◽  
Toru Marubayashi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Neoadjuvant Therapy ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Complete Response ◽  
Complete Excision ◽  
Content Type ◽  
Platinum Based Chemotherapy ◽  
Malignant Germ Cell Tumors ◽  
Fine Print

Object. The goal of this study was to confirm the effectiveness of our novel treatment strategy, neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy, which are performed before complete excision of residual tumor in patients with intracranial nongerminomatous malignant germ cell tumors (NGMGCTs). Methods. The authors treated 11 consecutive patients with NGMGCTs by applying NAT consisting of combined platinum-based chemotherapy and radiotherapy, followed by complete excision of residual tumors. The pretreatment diagnosis, based on tumor markers with or without biopsy, was yolk sac tumor in five patients, embryonal carcinoma in one patient, immature teratoma in one patient, and mixed germ cell tumor containing malignant tumor components in four patients. Among the 11 patients, NAT achieved a complete response in two and a partial response in six patients; two patients manifested no change and one suffered disease progression. Residual tumors that occurred post-NAT were surgically removed in nine patients. Of the 11 patients, 10 are currently alive without recurrence of their disease, 30 to 177 months (mean 96 months) after diagnosis. In one patient a leptomeningeal tumor recurred and he died of the disease 21 months after diagnosis. Conclusions. Neoadjuvant therapy, consisting of combined chemo- and radiotherapy, followed by complete excision of residual tumors is highly effective in patients with intracranial NGMGCTs.

scholarly journals Detection of Relapse by Tumor Markers Versus Imaging in Children and Adolescents With Nongerminomatous Malignant Germ Cell Tumors: A Report From the Children’s Oncology Group

2019 ◽  
Vol 37 (5) ◽  
pp. 396-402 ◽  
Author(s):  
Adriana Fonseca ◽  
Caihong Xia ◽  
Armando J. Lorenzo ◽  
Mark Krailo ◽  
Thomas A. Olson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Children And Adolescents ◽  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Initial Diagnosis ◽  
Phase Iii ◽  
Detection Methods ◽  
Pathology Reports ◽  
Malignant Germ Cell Tumors

PURPOSE To investigate relapse detection methods among children and adolescents with nongerminomatous malignant germ cell tumors (MGCTs) and to determine whether tumor markers alone might be sufficient for surveillance. METHODS We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs. The method used to detect relapse was assessed based on case report forms, tumor markers, imaging, and pathology reports. Relapses were classified into one of two categories on the basis of whether they were (1) detectable by tumor marker elevation or (2) not detectable by tumor markers. RESULTS A total of 302 patients were enrolled, and 284 patients had complete data for review. Seven patients had normal tumor markers at initial diagnosis, and none experienced a relapse. At a median follow-up of 5.3 years, 48 patients (16.9%) had experienced a relapse. After central review, 47 of 48 relapses (98%) were detected by tumor marker elevation. Of the 47 patients, 16 (33.3%) had abnormal tumor markers with normal/unknown imaging, 31 patients (64.6%) had abnormal tumor markers with abnormal imaging, and one patient (2.1%) had abnormal imaging with unknown marker levels at relapse. CONCLUSION Tumor marker elevation is a highly sensitive method of relapse surveillance, at least among children and adolescents with tumor marker elevation at initial diagnosis. Eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCT.

Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom.

1998 ◽  
Vol 16 (2) ◽  
pp. 716-724 ◽  
Author(s):  
S D Fosså ◽  
S B Kaye ◽  
G M Mead ◽  
M Cullen ◽  
R de Wit ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Combination Chemotherapy ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
Working Party ◽  
Phase Iii ◽  
Treatment Schedule ◽  
European Organization ◽  
Malignant Germ Cell Tumors

PURPOSE To determine the effect of r-metHu granulocyte colony-stimulating factor (G-CSF) on the proportion of patients with metastatic poor-prognosis malignant germ cell tumors who receive full dose-intensity combination chemotherapy. PATIENTS AND METHODS In a phase III study patients received six cycles of BEP/EP (etoposide, and cisplatin, plus or minus bleomycin) or six cycles of BOP/VIP-B (bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, bleomycin). A subset were secondarily randomized to receive or not receive filgrastim. Filgrastim 5 microg/kg/day was administered subcutaneously on days 3 through 9 after each BOP and on days 6 through 19 after each VIP, BEP, or EP cycle. RESULTS Eighty-five percent of 120 eligible patients randomized to filgrastim received at least six chemotherapy cycles compared with 70% of 130 patients randomized to not receive filgrastim (VCP = .003). Patients in the filgrastim-arm achieved significantly higher dose-intensities. Neutropenic fever occurred in 25 of 128 filgrastim-patients and in 38 of 129 non-filgrastim-patients (P = .052). Twelve and three toxic deaths occurred in the non-filgrastim- and filgrastim-arms, respectively. Nine of the 12 toxic deaths and all of the three toxic deaths were associated with febrile grade 4 neutropenia. Failure-free and overall survival were similar in both arms. CONCLUSION During combination chemotherapy in patients with malignant germ cell tumors, the routine use of filgrastim significantly improved the delivery of the planned treatment schedule without effect on failure-free or overall survival. The use of filgrastim was associated with a clinically important reduction in the number of toxic deaths, confined to the experimental intensified-chemotherapy schedule. This study does not support the routine use of filgrastim during standard chemotherapy with BEP.

Study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high-risk germ cell tumors: A Children's Oncology Group report

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10035-10035
Author(s):  
M. H. Malogolowkin ◽  
M. Krailo ◽  
L. A. Frazier ◽  
T. A. Olson
Keyword(s):  
High Risk ◽  
Germ Cell ◽  
Small Sample Size ◽  
Germ Cell Tumors ◽  
Small Sample ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Treatment Intensification ◽  
Grade 3 ◽  
Disease Free

10035 Background: In the intergroup high-risk germ cell tumors (HR-GCT) study (CCG-8882/POG-9049) patients with extragonadal GCT treated with high-dose cisplatin, etoposide, and bleomycin (HD-PEB) had a 2 year-EFS of 84% versus 74% for those treated with standard PEB (PEB), suggesting that treatment intensification might be beneficial. The goal of this study was to establish the maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide combined with PEB in untreated patients with HR-GCT. Methods: From July 2004 to August 2007, 19 eligible children and adolescents with stage III/IV extragonadal GCT received cisplatin 20 mg/m2/day × 5, etoposide 100 mg/m2/d × 5, bleomycin 15 mg/m2 on d1, and escalating doses of cyclophosphamide (1.2, 1.8 or 2.4 g/m2) on d1. DLT was defined as any grade 4 non-hematologic toxicity other than nausea and vomiting, fever and infection, and any non-hematologic grade 3 toxicity which had not reversed (< grade 2) within 28 days of treatment; or hematologic toxicity grade 3 or 4, which despite hematopoietic growth factor support, was not reversible within 28 days of treatment. Results: The toxicities reported were expected for this treatment regimen, protocol therapy was well tolerated and all 3 cyclophosphamide levels were feasible. Only 1 patient who had hyperglycemia was considered to have DLT by the institutional investigator. Fifteen of the 19 patients were removed from protocol therapy after 4 cycles of therapy; 11 were disease-free, 2 electively terminated protocol therapy, 1 patient was lost to follow-up, and 1 had progressive disease (PD). Four patients received 2 more cycles of C-PEB, of these 3 were disease-free and 1 had PD. The 2 year-EFS and OS were 71% (95% CI: 43–87%) and 88% (95% CI: 59–97%), respectively. Conclusions: The addition of cyclophosphamide to the standard PEB regimen is feasible and well tolerated at all dose levels used on this study. Due to the small sample size we cannot establish that the addition of cyclophosphamide to the standard PEB regimen is beneficial in increasing the EFS when compared to the standard PEB regimen. Further evaluation of this regimen is warranted. No significant financial relationships to disclose.

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