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.

A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.

1988 ◽  
Vol 6 (6) ◽  
pp. 1031-1040 ◽  
Author(s):  
R F Ozols ◽  
D C Ihde ◽  
W M Linehan ◽  
J Jacob ◽  
Y Ostchega ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dose Regimen ◽  
Standard Therapy ◽  
Poor Prognosis ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Dose Regimen ◽  
Disease Free

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.

8 SURGERY AFTER HIGH DOSE CHEMOTHERAPY FOR POOR RISK NON SEMINOMATOUS GERM CELL TUMORS (GCTs): A LONG FOLLOW UP

2010 ◽  
Vol 36 ◽  
pp. S97
Author(s):  
F. Morelli ◽  
A. Cisternino ◽  
A.M. Capotorto ◽  
G. Palomba ◽  
P. Setola ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Poor Risk

Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

1998 ◽  
Vol 16 (10) ◽  
pp. 3386-3391 ◽  
Author(s):  
C Kollmannsberger ◽  
J Beyer ◽  
J P Droz ◽  
A Harstrick ◽  
J T Hartmann ◽  
...  
Keyword(s):  
General Population ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Elevated Risk ◽  
High Dose ◽  
Secondary Acute Myeloid Leukemia ◽  
Low Incidence ◽  
Cell Support

PURPOSE High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT). PATIENTS AND METHODS The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. RESULTS A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. CONCLUSION Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

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]

Australia and New Zealand (ANZ) outcomes of high-dose chemotherapy and stem cell transplantation for relapsed or refractory germ cell tumors (GCT) from 1999 to 2019: Multicenter registry-based study with ABMTRR.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 382-382
Author(s):  
Elizabeth Anne Connolly ◽  
Andrew James Weickhardt ◽  
Peter S. Grimison ◽  
Gillian Heller ◽  
Jeremy Howard Lewin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Germ Cell ◽  
Bone Marrow Transplant ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Marrow Transplant ◽  
High Dose ◽  
Cell Transplant

382 Background: High dose chemotherapy (HDCT) with autologous stem-cell transplant (ASCT) is effective in advanced germ cell tumours (GCT) that are refractory to, or progress after, first-line therapies. Five-year overall survival in North American and European series range from 48-60%1,2,3. This study aimed to assess ANZ outcomes for quality assurance. Methods: Retrospective multi-centre audit of all male patients with GCT who underwent HDCT and ASCT from 1999-2019. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. Primary outcomes included overall and progression- free survival (OS, PFS). Results: 111 patients were identified at 13 centres, each treating a median (range) of 7 (1-27) patients. Median (range) age was 30 (14-68) years. 88 (79%) had testicular primary. 16% were pure seminoma. Median time from first diagnosis to first stem cell cycle was 11 months (range 3 months-38 years). Prior to ASCT, 35% had primary refractory disease and 65% had relapsed. IPFSG risk score was very low in 5%, low in 13%, intermediate in 36%, high in 25%, and very high in 21%. HDCT regimen was CE in 78% (as part of TI-CE regimen in 38%), Carbop-EC-T in 6%, ICE in 6%, CEC in 5% and other in 4%. 89% completed all planned HDCT and ASCT cycles. Five treatment related deaths occurred. Progressive disease on treatment occurred in 14%. At median follow-up time 4.4 years (95% CI: 2.9 to 6.0), 51% were disease-free, 13% alive with disease, 34% deceased. 3 patients displayed late progression over 2 years after ASCT. The estimated 1, 2 and 5-year PFS rates were 62%, 57% and 52% respectively and OS rates were 73%, 65% and 61%. Survival by IPFSG and IGCCG risk categories are displayed in the table below. Conclusions: This is the first registry-based audit of HDCT for metastatic GCT from ANZ, which has demonstrated our outcomes are comparable with best international practice. References: Gossi Bone Marrow Transplant 2018;53:820-825. Adra J Clin Onc 2017; 35(10):1096-1102. Feldman J Clin Onc 2010; 28(10):1706-13. [Table: see text]

Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: a Southeastern Cancer Study Group and Southwest Oncology Group protocol.

1991 ◽  
Vol 9 (7) ◽  
pp. 1163-1172 ◽  
Author(s):  
C R Nichols ◽  
S D Williams ◽  
P J Loehrer ◽  
F A Greco ◽  
E D Crawford ◽  
...  
Keyword(s):  
Germ Cell ◽  
Standard Dose ◽  
Cell Cancer ◽  
Single Agent ◽  
Prospective Trial ◽  
Germ Cell Tumors ◽  
Dose Intensity ◽  
Germ Cell Cancer ◽  
High Dose ◽  
Disease Free

Between 1984 and 1989, 159 patients presenting with advanced germ cell cancer were entered on a randomized clinical trial comparing the efficacy and toxicity of etoposide and bleomycin and either standard-dose cisplatin (20 mg/m2 daily for 5 days) or high-dose cisplatin (40 mg/m2 daily for 5 days). Of the 159 patients, 153 were assessable for toxicity and response. As expected, patients receiving the high-dose cisplatin regimen experienced significantly more neurotoxicity, ototoxicity, nausea and vomiting, and myelo-suppression. Four patients (3%) died related to therapy. Despite the toxicity encountered, dose intensity was maintained. Overall, 84% of patients in the high-dose arm received 80% or more of the projected dose of cisplatin, etoposide, and bleomycin; and 90% of patients on the standard-dose arm received 80% or more of the projected dose. Of the 76 eligible patients randomized to receive the high-dose cisplatin regimen, 52 (68%) became disease-free with chemotherapy alone or with subsequent resection of residual teratoma or cancer. Of the 77 patients randomized to the standard-dose arm, 56 (73%) became disease-free with chemotherapy alone or with surgery. Median follow-up is now 24 months. Eleven patients (three high-dose and eight standard-dose) relapsed from disease-free status. Overall, 74% of patients receiving the high-dose cisplatin regimen are alive, and 63% are continuously free of disease. Of the patients receiving the standard-dose cisplatin regimen, 74% are alive, and 61% are continuously free of disease. This randomized prospective trial in advanced germ cell cancer achieved dose intensity of the most active single agent in this disease. This dose intensity did not translate into an improved survival or cure. We conclude that dose escalation of cisplatin beyond standard doses results in excess toxicity with no accompanying therapeutic benefit.

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.

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