Salvage Treatment With Paclitaxel, Ifosfamide, and Cisplatin Plus High-Dose Carboplatin, Etoposide, and Thiotepa Followed by Autologous Stem-Cell Rescue in Patients With Relapsed or Refractory Germ Cell Cancer

2001 ◽  
Vol 19 (1) ◽  
pp. 81-88 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
J. Beyer ◽  
J. T. Hartmann ◽  
N. Schwella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Germ Cell ◽  
Tumor Progression ◽  
Stable Disease ◽  
Multiorgan Failure ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Salvage Treatment ◽  
High Dose ◽  
Salvage Regimen

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m2, ifosfamide 5 × 1.2 g/m2, and cisplatin 5 × 20 mg/m2 (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m2 × 3, etoposide 600 mg/m2 × 4, and thiotepa 150 to 250 mg/m2 × 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m2 and ifosfamide 5 g/m2 (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Individual Treatment with Stem Cell Rescue in Patients with Germ-Cell Tumors. Results of One Centrum.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5429-5429
Author(s):  
Jana Nepomucka ◽  
Jitka Abrahamova ◽  
Martin Foldyna ◽  
Zuzana Donatova ◽  
Drahomira Kordikova ◽  
...  
Keyword(s):  
Stem Cell ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Salvage Treatment ◽  
Individual Treatment ◽  
High Dose ◽  
Line Treatment ◽  
Stem Cell Rescue ◽  
The Individual

Abstract Background: Treatment with high dose chemotherapy and autologous stem cell rescue in pacients with poor risk germ cell tumors is still controversial. Results of multicentric randomized EBMT study IT 94 presented at ASCO 2002 show benefit in 1-year EFS in high dose arm (52% versus 48%), 3-year EFS was the same in both arms (53%) in salvage treatment. Individual treatment with stem cell rescue as upfront treatment offers a survival benefit. Methods:Autologous stem cell rescue was provided in our center, from September 1997 to May 2006 to 52 patients. High dose chemotherapy was indicated to 32 patients in salvage setting after 2nd line of treatment (VeIP) and to 20 patients as upfront treatment after 1st line treatment (BEP). Median age was 29 years and tumor markers were elevated: HCG in 9 pts, AFP in 13 pts. Stem cell mobilization was performed after the 3rd cycle of VeIP or BEP in combination with G-CSF. The amount of CD34+ cell/kg b.w. was between 2,0 – 13.4×106. High - dose conditioning regimen CARBOPEC (carboplatin 1600 – 2 200 mg/m2, etoposide 1 800mg/m2, cyclophosphamide 6 400 mg/m2) was used. The treatment was well tolerated without transplant - related mortality. Results: WHO criteria non - hematological toxicity was predominantly grade 2 to 3. Engraftment was rapid, recovery of hematopoiesis in neutrofils over 1.0×109/l and platelets over 50×109/l was reached an average on days +10 and +13 respectively. Additional post-transplant treatment for persistence, progression or relaps had 20 patients (8pts had 2nd line treatment VEIP, 12pts had 3nd line treatment with paclitaxel+gemcitabine and 5 pts had retroperitoneal lymfadenectomy). The follow - up period ranges from 3 to 99 months, at present 38 (73 %) patients are alive, 14 (27 %) pts died. Median TTP of all pts is 10 months, median OS of all pts is 39 months. Median DFS of surviving pts is 38 months. Conclusion: high-dose chemotherapy with autologous stem cell rescue in patients with poor risk germ cell tumors is feasible and beneficial method of the individual treatment. High-dose chemotherapy as upfront treatment for poor prognosis germ cell tumors and as salvage treatment in good risk pts seems to be good possibility of the individual treatment.

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.

Addition of darbepoetin alfa to sequential high-dose VIP chemotherapy for patients with advanced metastatic germ cell cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15026-e15026
Author(s):  
Joerg Thomas Hartmann ◽  
Bernd Metzner ◽  
Claudia Binder ◽  
Hans-Guenther Mergenthaler ◽  
Oliver Rick ◽  
...  
Keyword(s):  
Germ Cell ◽  
Darbepoetin Alfa ◽  
Poor Prognosis ◽  
Remission Rate ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Primary Objective ◽  
High Dose ◽  
Open Label ◽  
Similar Treatment

e15026 Background: High-dose VIP chemotherapy plus ABSCT given as first line treatment might be a strategy in patient with advanced germ cell tumors (GCT) with poor prognosis. The objective of the trial was to investigate the addition of darbepoetin alfa to HD-VIP in order to reduce anemia/red blood cell (RBC) transfusions. Methods: This was a randomized, open-label multicenter phase 2 study conducted in 20 hospitals. Darbepoetin 2.25 mcg/kg weekly or 500 mcg Q3W s.c., started with high dose VIP (dose level 6) was applied in arm B (arm A: HD-VIP alone). The primary objective was freedom from blood transfusions (FFT). Secondary objectives included objective remission rate (ORR) after chemotherapy, 24 mos PFS and OS, median course of hemoglobin (Hb) levels during 3 HD-VIP cycles as well as drug safety. Results: Between 7/2003 and 11/2008 108 pts were allocated to the study, and 106 were included in the intention-to-treat (ITT) analysis. By March 2011 the median follow-up time after randomization was 20 mos. Localisation of primary was gonadal in 66%, retroperitoneal in 19% and mediastinal in 14%s. A favourable treatment outcome (CR/NED/PR m-) in conjunction with secondary surgery (n = 76 pts) was achieved in 58% of pts with no difference between arms A and B. Overall FFT occurred in 2 pts (4.2%) in arm A and 3 pts (5.6%) in arm B, and in 23%/15%/15% and 15%/17%/19% of pts during cycles 1-3, respectively. No differences in baseline Hb, severity of anemia, no of RBC transfusions and area under the curve of Hb levels during HD-VIP was observed. Pts assigned to darbepoetin had similar treatment toxicity compared to those assigned to HD-VIP alone. 24-mos OS in arm A was 86.3% compared to 67.8% (p=.064) in Arm B. 2-year RFS was 66.8% in arm A vs 55.5% in Arm B (p=0.45). Darbopoetin was generally well tolerated with 2 pts discontinuing treatment due to thrombosis. Since compliance to study protocol was generally poor (6 out of 55 pts never received study drug during HD-VIP) a per-protocol analysis is in preparation. Conclusions: Based on ITT analysis, the addition of darbepoetin alfa to the high dose regimen compared to HD-VIP alone does not appear to impact on FFT, ORR, and 2-year survival rate in poor prognosis GCT pts (NCT00204633).

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