Salvage Therapy in Patients with Germ Cell Tumors

2015 ◽  
pp. e259-e261 ◽  
Author(s):  
Lawrence H. Einhorn
Keyword(s):  
Combination Chemotherapy ◽  
Salvage Therapy ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
Liver Function Tests ◽  
High Dose Chemotherapy ◽  
Cross Reactivity ◽  
High Dose ◽  
Metastatic Solid Tumor ◽  
Proper Interpretation

Testicular cancer is the most curable metastatic solid tumor. Initial chemotherapy is evidence based with risk stratification into three prognostic categories: good, intermediate, and advanced disease. Guidelines for disease management following progression after initial cisplatin combination chemotherapy are less clear. Options include salvage surgery for patients with anatomically confined relapse, standard-dose cisplatin combination chemotherapy, or high-dose chemotherapy with carboplatin plus etoposide with peripheral blood stem cell transplantation. Proper interpretation of a presumed relapse can be complicated. Growing masses on imaging studies might reflect a growing teratoma. Persistent elevations of serum human chorionic gonadotropin (hCG) or alpha fetoprotein (AFP) are only an indication for salvage therapy if there is a definitive rise in the tumor marker. Elevated and rising serum hCG as the only evidence of recurrence can be because of cross reactivity with luteinizing hormone or usage of marijuana rather than progressive cancer. Elevated liver function tests can cause rising serum AFP.

scholarly journals Salvage Therapy for Patients With Germ Cell Tumor

2016 ◽  
Vol 12 (5) ◽  
pp. 437-443 ◽  
Author(s):  
Sawsan Rashdan ◽  
Lawrence H. Einhorn
Keyword(s):  
Survival Rate ◽  
Germ Cell ◽  
Combination Chemotherapy ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

The introduction of cisplatin combination chemotherapy, 40 years ago, transformed metastatic testicular germ cell tumors from an almost uniformly fatal disease into a model for a curable neoplasm. Before the era of platinum combination chemotherapy, the 5-year survival rate among men with metastatic testicular germ cell tumors was 5% to 10%. Currently, the 5-year survival rate is 80% for patients with metastatic disease and 95% overall. Despite the substantial advances in the treatment of germ cell tumors, 20% to 30% of patients will relapse after first-line chemotherapy and will require additional salvage therapies. Standard-dose or high-dose chemotherapy can cure ≤ 50% of these patients. Relapses after high-dose chemotherapy generally carry a poor prognosis; however, cure is still possible in a small percentage of patients by using further salvage chemotherapy or salvage surgery.

Comparison of standard versus high dose of paclitaxel with ifosfamide and cisplatin (TIP) in salvage therapy of germ cell tumors (GCTs).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15028-e15028
Author(s):  
Jozef Mardiak ◽  
Michal Mego ◽  
Viera Miskovska ◽  
Zuzana Sycova-Mila ◽  
Jana Obertova ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Primary Tumor Site ◽  
Prognostic Features ◽  
First Relapse

e15028 Background: Currently, TIP with higher dose of paclitaxel (250mg/m2) is considered standard salvage chemotherapy in GCTs with good prognostic features. However, until 2007, we utilized regimen with standard dose of paclitaxel (175mg/m2). The aim of this study was to compare the efficacy of TIP with the standard versus higher dose of paclitaxel as first salvage therapy for patients with relapsed GCTs. Methods: This retrospective study included 64 patients with relapsed GCTs treated with TIP as first salvage therapy between 1998 and 2010 in two major cancer centers in Slovakia. Forty five patients (70%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen). Four cycles of standard dose (175mg/m2, 37 patients) or higher dose (250 mg/m2, 27 patients) of paclitaxel (day 1) with ifosfamide 1.2 g/m2 (day 1-5) and cisplatin 20 mg/m2 (day 1-5) were given 21 days apart with G-CSF support, followed by resection of resectable radiographic residua. Results: Nineteen of 37 (51%) patients treated with standard dose of paclitaxel achieved favourable response (complete remission or partial remission with negative serum tumor markers) compared to 20 of 27 (74%) patients treated with higher dose of paclitaxel (p = 0.07). In median follow-up of 23.9 months 37 patients (58%) experienced disease relapse and 33 (52%) patients died. Patients treated with higher dose of paclitaxel had better progression-free survival (median: not reached vs. 7 months, HR = 0.54, 0.28 - 1.04; p = 0.06) and overall survival (median: not reached vs. 33 months, HR = 0.69, 0.34-1.39; p = 0.31) compared to patients treated with standard dose of paclitaxel. Conclusions: Our data support the hypothesis that higher dose of paclitaxel with ifosfamide and cisplatin is associated with better outcome compared to standard dose of paclitaxel in patients with relapsed GCTs treated in first relapse.

Phase II-study of sequential high-dose-chemotherapy with paclitaxel, ifosfamide, carboplatin, etoposide( P-ICE) in patients with relapsed or refractory germ cell tumors (GCT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4552-4552
Author(s):  
Thomas Kegel ◽  
Franziska Cygon ◽  
Fabian Maximilian Meinert ◽  
Khaled Hammad ◽  
Frank Steinbach ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Bone Marrow Toxicity ◽  
Good Tolerability ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Ecog Ps

4552 Background: High-dose chemotherapy (HD-CTx) is an active option for salvage chemotherapy in patients (pts) with refractory or relapsed GCT. All previous trials with HD-CTx used one or two cycles of high dose chemotherapy (CTx) including 2 or a maximum of 3 drugs. Another potentially more active option is the application of four sequential HD-CTx cycles (Schmoll et al, JCO 2003). Methods: We conducted a phase II trial of 1(-2) cycle(s) induction CTx with standard dose P-ICE (Paclitaxel 135mg/m² d1, Ifosfamide 1500mg/m² d1-3, Carboplatin 150mg/m² d1-3, Etoposide 150mg/m² d1-3), followed by 4 sequential cycles of HD-P-ICE (Paclitaxel 200mg/m² d1, Ifosfamide 3300mg/m² d1-3, Carboplatin 330mg/m² d1-3, Etoposide 330mg/m² d1-3). Eligibility criteria: relapse or progression under one or more induction CTx, ECOG PS (0-1), Creatinine-clearance > 30ml/min, adaequate liver function, measurable tumor or at least marker-elevation. Results: 37 pts entered the trial and 33 are evaluable (4 pts never received HD-CTx due to lack of stem cells (3) or medical reasons (1)). Prior CTx:1 (N = 26), 2 (N = 4), 3 (N = 3); primary extragonadal: 6; seminoma/ non-seminoma 5/28; ECOG-PS: 0 (19), 1 (14). Response rate: CR/NED 17 (51.5%), CR/NED/PR-/SD- with marker normalization 21 (63.6%), PD 12 (36.4%). DFS of CR/NED: median 59 (8-105) months; RFS of all favourable responders 60 (8-105) months, PFS total 46 (2-105) months. OS for all pts. 51 (6-105) months, OS Favourable Responders: 65 (23 – 105), Nonfavourable Responders: 11 (6-27) months,. Toxicity was tolerable without treatment related death, with mainly grade 4 bone-marrow toxicity and grade 2 mucositis and/or diarrhea. Conclusions: Sequential HD-CTx with one cycle of SD-P-ICE and four cycles HD-CTx is feasible with acceptable toxicity and favourable efficacy. Sequential HD-CTx using the four most active drugs might be a potentially option for this pts-population due to good tolerability, applicability and interesting long-term outcome. Comparison of the standard approach with 1 to 3 sequential high dose cycles of Carboplatin/Etoposide is ongoing (TIGER-Trial). Clinical trial information: EUDRA-CT: 2006-006004-11.

Survival and toxicity outcomes in patients age 40 or older with relapsed metastatic germ cell tumors (mGCT) treated with high-dose chemotherapy (HDCT) and autologous peripheral-blood stem cell transplant (PBSCT).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 522-522
Author(s):  
Nabil Adra ◽  
Costantine Albany ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Dannillo Pereira ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Indiana University ◽  
Free Survival ◽  
Kaplan Meier

522 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity which can be more pronounced in older patients. We report survival and toxicity outcomes in pts with relapsed mGCT age ≥ 40 at time of HDCT. Methods: 440 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University (IU) between 2004-2017 per our previous reported regimen (N Engl J Med 2007; 357: 340-8). Kaplan-Meier methods were used for progression free survival (PFS) analysis. Results: 110 pts were age ≥ 40 while 330 pts were age < 40. Among pts age ≥ 40, median AFP was 6.6 (range, 1-2,709) and median hCG was 5.3 (range, 1-42, 453). Of the 110 pts age ≥ 40, 75 had complete remission without relapse during a median follow-up of 23 months. There were 3 treatment-related deaths. Conclusions: HDCT plus PBSCT is safe and effective salvage therapy in pts age ≥ 40 with relapsed mGCT. [Table: see text]

scholarly journals P14.05 Treatment of relapsing patients with intracranial germ cell tumors: the French experience

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii67-iii67
Author(s):  
L Callec ◽  
C Patte ◽  
A Lardy-Cleaud ◽  
L Vignon ◽  
C Alapetite ◽  
...  
Keyword(s):  
Germ Cell ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Stem Cell Rescue ◽  
French Experience ◽  
Intracranial Germ Cell Tumors ◽  
Group A ◽  
Group B

Abstract BACKGROUND Optimal strategy for treatment of relapsing intracranial malignant germ cell tumors remains ill-defined. Authors describe the French experience over a 25-year period. MATERIAL AND METHODS Relapsing patients were retrieved by their participation in the SFOP-TGM 90-92 or GCT 96 protocols or from National Childhood Solid Tumour Registry. RESULTS The cohort included Group A: documented germinomas (n=14), Group B: patients treated as germinomas without histopathological proof (n=5) and Group C: secreting germ cell tumours (n=25). Patients all received standard dose chemotherapy, and some high dose chemotherapy (VP16 Thiotepa with stem cell rescue) and/or various type of radiation. The 5 year EFS and OS post relapse are: 79%[47 to 93%] and 86% [54 to 96%] respectively in group A, 20% [1 to 58%] and 80% [20 to 97%] respectively in group B, 56% [35 to 73%] and 60% [38 to 76%] respectively in group C. Among 14 Group A patients, 7/12 receiving high dose versus 3/3 receiving standard dose chemotherapy, and 9/11 re-irradiated versus 1/3 not re-irradiated are CR2. Among 21 Group C patients. who had received radiation in first line, 10/15 receiving high dose versus 1/6 receiving standard dose chemotherapy, and 7/11 re-irradiated versus 4/10 not re-irradiated are CR2. CONCLUSION The outcome of relapsing germinoma is favourable and intensity of second line remains matter of debate. High dose chemotherapy with radiotherapy, when feasible, should remain the reference for treatment of a relapsed non germinoma, though more active treatments are warranted.

Randomized Comparison of Combination Chemotherapy With Etoposide, Bleomycin, and Either High-Dose or Standard-Dose Cisplatin in Children and Adolescents With High-Risk Malignant Germ Cell Tumors: A Pediatric Intergroup Study—Pediatric Oncology Group 9049 and Children's Cancer Group 8882

2004 ◽  
Vol 22 (13) ◽  
pp. 2691-2700 ◽  
Author(s):  
Barbara Cushing ◽  
Roger Giller ◽  
John W. Cullen ◽  
Neyssa M. Marina ◽  
Stephen J. Lauer ◽  
...  
Keyword(s):  
High Risk ◽  
Pediatric Oncology ◽  
Combination Chemotherapy ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose ◽  
Oncology Group ◽  
Cancer Group ◽  
Pediatric Oncology Group ◽  
Malignant Germ Cell Tumors

Purpose To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity. Patients and Methods Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen. Results One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6% ± 3.6% v 80.5% ± 4.8% for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7% ± 3.3% v PEB 86.0% ± 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB. Conclusion Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.

Salvage high-dose chemotherapy for primary mediastinal nonseminomatous germ cell tumors: Single institute experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15503-e15503
Author(s):  
John WT Walker ◽  
Scott A. North ◽  
Naveen S. Basappa ◽  
Peter M. Venner
Keyword(s):  
Germ Cell ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Small Sample ◽  
Cancer Center ◽  
High Dose ◽  
Cell Transplant ◽  
Disease Free

e15503 Background: Primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) bear a worse prognosis than stage-matched testicular primaries, with a five year survival rate of 50%. In contrast to relapsed testicular NSGCT, retrospective analyses have not shown benefit to high-dose chemotherapy and autologous stem-cell transplant (HDCT/ ASCT) in PMNSGCT patients. Since publication of these studies, advancements in treatment regimens and supportive care have occurred, with emerging evidence suggesting HDCT/ASCT may benefit patients with PMNSGCT - both as first-line sequential treatment after standard-dose chemotherapy and at relapse. Objectives: Review the experience of patients presenting with PMNSGCT to a regional referral cancer center as a quality control assessment. Assess the benefit of salvage HDCT/ASCT to relapsed PMNSGCT patients. Methods: Patients presenting with PMNSGCT from 1980-2010 were abstracted from a Provincial cancer registry and records were retrospectively reviewed. Data includes patient demographics, cancer treatments and outcomes. Results: Fourteen male patients (median age 29; range: 17-54 years) with PMNSGCT were identified. Seven of 13 (54%) patients remain continuously disease-free with 1 patient lost to follow-up. Mean duration of follow-up in these patients is 57 (34-100) months. Three patients died having received ≤ 1 cycle of chemotherapy; exclusion of these patients results in a treatment failure rate of 30%. Six of the 7 cancer-free patients required salvage surgery. Three patients received tandem HDCT/ASCT (carboplatin 550 mg/m2 and etoposide 150 mg/m2daily for 4 days) at subsequent relapse despite second-line chemotherapy. Two remain disease-free at 45 and 74 months respectively, while the third patient died of their disease 14 months post-transplant. Conclusions: Our experience with PMNSGCT is generally consistent with published outcomes in that ≈50% of patients are cured. However, in this series 2/3 heavily pretreated patients were salvaged with HDCT/ASCT, refuting the published historical experience. This study is limited by its small sample size, but provides impetus to re-examine HDCT/ASCT for high-risk patients.

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