High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables.

1996 ◽  
Vol 14 (10) ◽  
pp. 2638-2645 ◽  
Author(s):  
J Beyer ◽  
A Kramar ◽  
R Mandanas ◽  
W Linkesch ◽  
A Greinix ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
The United States ◽  
High Dose Chemotherapy ◽  
Hematopoietic Progenitor Cell ◽  
Risk Category ◽  
High Dose ◽  
Prognostic Variables ◽  
Increased Risk

PURPOSE To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

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.

Germline Polymorphisms Provide Strong Prognostic Information in Intermediate Risk Acute Myeloblastic Leukemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 398-398
Author(s):  
Alvaro Urbano-Ispizua ◽  
Salut Brunet ◽  
Mariano Monzo ◽  
Granada Perea ◽  
Alfons Navarro ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Rank Test ◽  
P Value ◽  
Risk Category ◽  
High Dose ◽  
Intermediate Risk ◽  
Prognostic Information ◽  
Prognostic Variables ◽  
Increased Risk

Abstract In this study we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways (GSTT1, SULT1C2, CD-EX, TOP2A, SXR-1, SXR-2), DNA repair (XPD, XPA, XPG, ERCC1), angiogenesis (VEGF-1, VEGF-2), and multidrug resistance (MDR1-1, MDR1-2) predict clinical outcome in patients with AML. Two hundred adult patients ≤60 year-old with primary AML (M3 excluded), enrolled in the AML-99 protocol of the CETLAM group between November-98 and July-03, have been studied. Induction therapy consisted of idarubicin, intermediate dose ara-C (IDAC) and VP16. Intensification included mitoxantrone and IDAC. Patients were following treated with high-dose ara-C or transplantation depending on the risk category. According to the MRC cytogenetic classification, 32 patients had a favourable karyotype, 23 had abnormalities indicating poor prognosis, and 110 patients were included in the intermediate prognosis (IP) group. We focused on IP group patients with the aim of improving its prognostic stratification. The characteristics considered were: age (<50 years vs ≥50), WBC (≤20x109/l vs >20x109/l), FAB classification, MLL rearrangement, internal tandem duplication of FLT3 (ITD-FLT3), induction courses to achieve complete remission (CR) (1 vs 2), and germline polymorphisms of the above-mentioned genes. Prognostic variables in the univariate analysis (Kaplan-Meier method) with a p value ≤0.2 (log-rank test) were included for the multivariate analysis (proportional hazard method). Of the 110 patients included in the IP group, 86 (78%) achieved a CR, 11 (10%) were chemoresistant and 13 (12%) died during induction. After a median follow-up of alive patients of 24 months (range 5–64), overall survival was of 31% at 5 years. In the multivariate analysis, adverse prognostic variables for survival were polymorphism of XPA (RR=3.4; p=0.02) and of MDR1-1 (RR=2.1; p=0.02), and WBC >20x109/l (RR=2.1; p=0.02). Increased risk of relapse was associated with polymorphism of SULT1C2 (RR 4.1; p=0.004), ITD-FLT3 (RR 3.3; p=0.003), VEGF2 (RR 2.8; p=0.04) and MDR1-1 (RR 2.4; p=0.02). Finally, in the multivariate analysis for refractoriness to chemotherapy, XPA polymorphism was the only independent factor increasing the risk (RR=14; p=0.02). In conclusion, germline polymorphisms, which can easily be analyzed from DNA of peripheral blood, have independent prognostic value in intermediate risk AML.

scholarly journals Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience

2005 ◽  
Vol 16 (1) ◽  
pp. 146-151 ◽  
Author(s):  
U. De Giorgi ◽  
T. Demirer ◽  
H. Wandt ◽  
C. Taverna ◽  
W. Siegert ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Second Line

High-Dose Chemotherapy for Recurrent Ovarian Germ Cell Tumors

2015 ◽  
Vol 33 (2) ◽  
pp. 226-227 ◽  
Author(s):  
Natraj Reddy Ammakkanavar ◽  
Daniela Matei ◽  
Rafat Abonour ◽  
Lawrence H. Einhorn
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose

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.

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