Salvage chemotherapy with high dose carboplatin + etoposide (HDCE) and peripheral blood stem cell transplant (PBSCT) in patients with germ cell tumors (GCT)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4549-4549 ◽  
Author(s):  
L. H. Einhorn ◽  
S. Williams ◽  
R. Abonour
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Salvage Chemotherapy ◽  
Late Relapse ◽  
High Dose ◽  
Cell Transplant ◽  
Cure Rate ◽  
Indiana University ◽  
Prior Therapy ◽  
Hematopoietic Recovery

4549 Background: We began studies with HDCE for patients (pts.) with recurrent GCTs 20 years ago. During the past decade, better supportive care and use of PBSCT allowed outpatient therapy and more rapid hematopoietic recovery between the 2 courses of HDCE. Methods: Retrospective review of 184 consecutive pts. treated with HDCE at Indiana University from 2–96 to 12–04. Late relapse (> 2 years from prior therapy) and primary mediastinal non-seminomatous germ cell tumor pts. were not offered HDCE. Cytoreduction with 0–2 courses of vinblastine + ifosfamide + cisplatin preceded HDCE. C dosage was 700 mg/M2 × 3 and E 750 mg/M2 × 3. A second course was given after hematologic recovery. Results: Toxicity was as previously described (JCO 18:3346, 2000). There were 3 drug- related mortalities. An additional 3 patients developed AML (2 fatal), and 1 glioma following CNS XRT for metastases. 11 pts. did not receive second course (8 due to progression or HDCE mortality). Median time to second course HDCE was 28 days (range 20 to 42). 116 of 184 pts. are alive and continuously (cont) NED (63%) with median followup 42 months (range 11 to 118). 113 (97%) of these are 12+ months NED. 5 additional pts. are currently NED with further therapy. Results are tabulated below. Conclusions: HDCE has a high cure rate with acceptable toxicity as salvage therapy for GCT pts. [Table: see text] [Table: see text]

Can patients (pts.) with refractory germ cell tumors (GCT) be cured after progression following high dose chemotherapy (HDCT) with tandem transplant? Results with paclitaxel + gemcitabine

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4588-4588
Author(s):  
D. A. Lewis ◽  
M. J. Brames ◽  
L. H. Einhorn
Keyword(s):  
Germ Cell ◽  
Objective Response ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Indiana University

4588 Background: A previously published ECOG study of paclitaxel (P) plus gemcitabine (G) in refractory germ cell tumors achieved a 21% response rate (6 of 28 pts.) (JCO 20:1859, 2002). Two patients are continuously NED for 4+ years. Neither had prior HDCT. High dose salvage chemotherapy with carboplatin + etoposide and peripheral blood stem cell transplant has curative potential. Subsequent chemotherapy after progression following HDCT has only rarely achieved durable remission. We have retrospectively reviewed pts. treated at Indiana University with P + G after failure to cure with initial cisplatin combination chemotherapy and salvage HDCT (± other salvage regimens). Methods: 184 patients received salvage HDCT from February 1996 to December 2004. After further progression, 33 pts. were treated with P 100 mg/M2 over 1 hour and G 1000 mg/M2 over 30 minutes days 1, 8, and 15 every 4 weeks for a maximum of 6 courses. Pts. were ineligible if they received prior P or G. 26 pts. received P + G as 3rd line, 6 as 4th line and 1 as 5th line chemotherapy. Results: Toxicity was primarily myelosuppression and neuropathy, as previously described with P + G (JCO 20:1859, 2002). There was no treatment related mortality. 10 of 33 pts. achieved objective response including 4 partial (2 to 6 months duration) and 6 complete responses (C.R.). 4 of the 6 C.R.s are continuously NED with P + G alone at 14+, 34+, 44+, and 45+ months from start of P + G. One additional C.R. is currently NED 54+ months after P + G, with 2 subsequent resections of carcinoma. Conclusions: Long-term disease free survival and potential cure is possible with P + G in this patient population after progression following HDCT. [Table: see text]

Outcomes of patients with germ cell tumors diagnosed with stage I disease who subsequently received high dose chemotherapy (HDCT) with peripheral stem cell transplant (PBSCT) following failure of initial therapy for metastatic disease: The Indiana University experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5029-5029
Author(s):  
Stephen B Benzinger ◽  
Ryan Ashkar ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Nabil Adra ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Stage I ◽  
Risk Category ◽  
High Dose ◽  
Cell Transplant ◽  
Indiana University ◽  
First Line ◽  
Strict Adherence

5029 Background: Pts with stage I testicular germ cell tumors (GCT) have a 15-year DFS of 99%. However, 1% are not cured, despite orchiectomy and systemic therapy at relapse. Predictive variables for relapse in this small population have not been identified. Methods: Pts undergoing HDCT with PBSCT as salvage therapy for relapsed GCT after an initial diagnosis of stage I disease managed with orchiectomy and surveillance were evaluated from a database at Indiana University. Patient demographics, disease characteristics, adherence to standard surveillance guidelines for stage I disease, prognostic variables, treatment received in the first-line setting, pattern of relapse, and outcomes were analyzed. Results: From 1/92 to 10/19, 71 pts (34 seminoma, 37 NSGCT) initially diagnosed with stage I GCT managed with orchiectomy and surveillance but subsequently relapsed and eventually required HDCT with PBSCT were identified. Median f/u time was 5.1 years (range, 1.1-18.8). Median age was 34.1. First-line chemo consisted of BEP or EP in most pts. Risk category at relapse: good/intermediate/poor (52/8/11). Pattern of initial relapse included 22 (seminoma n=13, NSGCT n=9) with RPLN only. Relapse and death after HDCT occurred in 2 of these 22 pts. Strict adherence to standard surveillance guidelines was observed in 62/71 pts. Relapse and/or death after HDCT occurred in 3 of 9 with inadequate surveillance follow-up. At a minimum of 1 yr follow-up, 54 of 71 (76%) remain alive, including 47 (66%) who have no evidence of disease (NED). Conclusions: Most patients in this series progressed despite appropriate surveillance and first-line chemotherapy. Pattern of relapse was also not indicative of further progression in most patients. Further investigation should evaluate disease biology that puts patients with potentially easily curable disease at risk of multiple relapses.[Table: see text]

Long-Term Survival After High-Dose Salvage Chemotherapy for Germ Cell Malignancies With Adverse Prognostic Variables

2003 ◽  
Vol 21 (22) ◽  
pp. 4100-4104 ◽  
Author(s):  
Daniel A. Vaena ◽  
Rafat Abonour ◽  
Lawrence H. Einhorn
Keyword(s):  
Germ Cell ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Prognostic Variables ◽  
Term Survival ◽  
Risk Patients ◽  
Platinum Refractory

Purpose: Independent prognostic variables for patients undergoing high-dose chemotherapy (HDCT) as salvage modality for germ cell tumors (GCT) were previously described, and a score was created. Patients with more than 2 points had a poor prognosis. However, these data were from patients treated from 1984 to 1993, and most received a single HDCT course. In this study, we evaluated outcomes at Indiana University and determined the applicability of the Beyer score to contemporary poor-risk patients. Patients and Methods: We performed a retrospective analysis of patients who received salvage HDCT between 1988 and 2001 and had at least one of the following characteristics: platinum-refractory or absolutely platinum-refractory GCT, primary mediastinal nonseminomatous GCT (PMNSGCT), human chorionic gonadotropin (HCG) ≥ 1,000 mU/mL or alpha-fetoprotein (AFP) ≥ 1,000 ng/mL before HDCT. Primary end points were overall and 2-year failure-free survival (FFS). Results: Eighty patients were identified. Fifty-six were platinum refractory, 23 had a Beyer score greater than 2, and 13 had PMNSGCT. Fifty-six patients received two HDCT courses. HDCT included carboplatin and etoposide. Forty-three patients received HDCT as first salvage modality. Median overall survival was 14.7 months. The 2-year FFS was 32%. No relapses have occurred after 2 years from HDCT. Patients with greater than 2 points in the Beyer score, platinum-refractory patients, and patients with HCG ≥ 1,000 mU/mL, AFP ≥ 1,000 ng/mL, and PMNSGCT had 2-year FFS of 30%, 37%, 26%, 18%, and 0%, respectively. Conclusion: Results with PMNSGCT remained poor. However, other patients with poor prognosis should not be denied an attempt at curative salvage HDCT.

A 10-year retrospective review of germ cell tumors not cured with cisplatin-based chemotherapy.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 325-325
Author(s):  
Elizabeth O'Donnell ◽  
Kathryn P. Gray ◽  
Michelle S. Hirsch ◽  
Praful Ravi ◽  
Clair Beard ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Retrospective Review ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Cell Tumor ◽  
Smoking History ◽  
Late Relapse ◽  
High Dose

325 Background: In 2011, there were about 8260 cases of Germ Cell Tumor (GCT) diagnosed in the US, of those, 350 or 4% will die of their disease. We sought to review our experience with a 10-year cohort of 819 patients treated for GCT at Dana-Farber and synthesize the cumulative findings of those who died from their disease specifically looking for different sub-types of incurable GCTs. Methods: Retrospective review of 819 germ-cell tumors treated in our center between 2000 and 2010 to identify patients not cured with cisplatin-based chemotherapy. Inclusion criteria were men over the age of 18 treated for malignant germ cell tumor between 2000 and 2010 at the Dana-Farber Cancer Institute that died from their disease. The outcomes of interest were smoking history, extent of disease at diagnosis, primary site of disease, histology, presence of lymphovascular invasion, outcomes to first- and second-line therapies, treatment with high dose chemotherapy (HDC), late relapse, brain metastases, and presence or absence of transformed teratoma as cause of death. Results: 38 men were identified. Median age 35. More than half had a smoking history. 3 presented with clinical stage 1 disease, 8 good-risk metastatic disease, 4 intermediate-risk and 22 poor-risk at diagnosis. The majority (28) had testicular primaries, 7 mediastinal, one pituitary, one retroperitoneal and one unknown. 21 of 48 had complete responses to first-line therapy. 4 received HDC for relapsed disease. 10 relapsed after 2 years of disease-free survival. 7 died of transformed teratoma. 63% progressed directly through cisplatin-based chemotherapy and died as a result of non-teratomatous germ cell tumor burden. 18% died from unresectable or transformed teratoma and 26% died after suffering a late relapse of disease. Conclusions: Within the cohort of patient who died from their GCTs there are three distinct biological subtypes – the majority is platinum-refractory germ cell tumor while unresectable/transformed teratoma and late relapse make up the remainder. Understanding the unique biology of these disease states compared with curable disease may provide informative insights into chemotherapy resistance for cancer in general.

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]

Late Relapses of Germ Cell Malignancies: Incidence, Management, and Prognosis

2006 ◽  
Vol 24 (35) ◽  
pp. 5503-5511 ◽  
Author(s):  
Jan Oldenburg ◽  
Jarad M. Martin ◽  
Sophie D. Fosså
Keyword(s):  
Germ Cell ◽  
Initial Treatment ◽  
Relevant Literature ◽  
Tumor Biology ◽  
Germ Cell Tumors ◽  
High Volume ◽  
Salvage Chemotherapy ◽  
Pooled Analysis ◽  
Late Relapse ◽  
Cancer Specific Survival

Late relapses of malignant germ cell tumors (MGCTs) are rare and occur, by definition, 2 years or later after successful treatment. They represent a major challenge of today's treatment of MGCTs. Because of the rarity and heterogeneity of late relapses, many aspects of their main characteristics remain obscure. We present relevant literature on relapsing MGCTs to highlight the following issues: incidence, impact of initial treatment on the subsequent risk of late relapse, treatment, and survival. In a pooled analysis, the incidence is 1.4% and 3.2% in seminoma and nonseminoma patients, respectively. The predominant site of relapse is the retroperitoneal space in both histologic types. The initial treatment appears to be important for the risk and localization of late relapses. The treatment of late relapses should be based on a representative presalvage biopsy and includes radical surgery and salvage chemotherapy in most cases. Five-year cancer-specific survival is above 50% in the recent large series and reaches 100% in case of single-site teratoma. Diagnosis and treatment of late-relapsing MGCT patients is challenging and should be performed in experienced centers only. Referral of late-relapsing patients to high-volume institutions ensures the best chances of cure and enables increasing understanding of tumor biology and the clinical course of these patients.

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