Literature DB >> 21059637

A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974).

G Daugaard1, I Skoneczna2, N Aass3, R De Wit4, M De Santis5, H Dumez6, S Marreaud7, L Collette7, J R G Lluch8, C Bokemeyer9, H J Schmoll10.   

Abstract

BACKGROUND: To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC). PATIENT AND METHODS: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual.
RESULTS: One hundred thirty-one patients were included in this analysis. The complete response rates in the HD-CT and in the BEP arm did not differ: (intention to treat) 44.6% versus 33.3% (P = 0.18). There was no difference in FFS between the two treatment arms (P = 0.057, 66 events). At 2 years, the FFS rate was 44.8% [95% confidence interval (CI) 32.5-56.4] and 58.2%, respectively (95% CI 48.0-71.9); but this 16.3% (standard deviation 7.5%) difference was not statistically significant (P = 0.060). Overall survival did not differ between the two groups (log-rank P > 0.1, 47 deaths).
CONCLUSION: This study could not demonstrate that high-dose chemotherapy given as part of first-line therapy improves outcome in patients with poor-prognosis GCC.

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Year:  2010        PMID: 21059637      PMCID: PMC3082158          DOI: 10.1093/annonc/mdq575

Source DB:  PubMed          Journal:  Ann Oncol        ISSN: 0923-7534            Impact factor:   32.976


  12 in total

1.  Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial.

Authors:  S J Pocock; R Simon
Journal:  Biometrics       Date:  1975-03       Impact factor: 2.571

2.  International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group.

Authors: 
Journal:  J Clin Oncol       Date:  1997-02       Impact factor: 44.544

3.  First-line high-dose chemotherapy compared with standard-dose PEB/VIP chemotherapy in patients with advanced germ cell tumors: A multivariate and matched-pair analysis.

Authors:  C Bokemeyer; C Kollmannsberger; C Meisner; A Harstrick; J Beyer; B Metzner; J T Hartmann; H J Schmoll; L Einhorn; L Kanz; C Nichols
Journal:  J Clin Oncol       Date:  1999-11       Impact factor: 44.544

4.  Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party.

Authors:  L Collette; R J Sylvester; S P Stenning; S D Fossa; G M Mead; R de Wit; P H de Mulder; N Neymark; E Lallemand; S B Kaye
Journal:  J Natl Cancer Inst       Date:  1999-05-19       Impact factor: 13.506

5.  Predicting outcome to chemotherapy in patients with germ cell tumors: the value of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein during therapy.

Authors:  M Mazumdar; D F Bajorin; J Bacik; G Higgins; R J Motzer; G J Bosl
Journal:  J Clin Oncol       Date:  2001-05-01       Impact factor: 44.544

6.  Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation.

Authors:  C R Nichols; G Tricot; S D Williams; K van Besien; P J Loehrer; B J Roth; L Akard; R Hoffman; R Goulet; S N Wolff
Journal:  J Clin Oncol       Date:  1989-07       Impact factor: 44.544

7.  Long-term results of first-line sequential high-dose etoposide, ifosfamide, and cisplatin chemotherapy plus autologous stem cell support for patients with advanced metastatic germ cell cancer: an extended phase I/II study of the German Testicular Cancer Study Group.

Authors:  H-J Schmoll; C Kollmannsberger; B Metzner; J T Hartmann; N Schleucher; P Schöffski; J Schleicher; O Rick; J Beyer; D Hossfeld; L Kanz; W E Berdel; R Andreesen; C Bokemeyer
Journal:  J Clin Oncol       Date:  2003-10-20       Impact factor: 44.544

8.  High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors.

Authors:  Lawrence H Einhorn; Stephen D Williams; Amy Chamness; Mary J Brames; Susan M Perkins; Rafat Abonour
Journal:  N Engl J Med       Date:  2007-07-26       Impact factor: 91.245

9.  A phase I/II study of a stepwise dose-escalated regimen of cisplatin, etoposide and ifosfamide plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced germ cell tumours.

Authors:  C Bokemeyer; H J Schmoll; A Harstrick; H J Illiger; B Metzner; U Räth; J Hohnloser; C Clemm; W Berdel; W Siegert
Journal:  Eur J Cancer       Date:  1993       Impact factor: 9.162

10.  Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group.

Authors:  Anja Lorch; Christian Kollmannsberger; Joerg Thomas Hartmann; Bernd Metzner; Ingo G H Schmidt-Wolf; Wolfgang E Berdel; Florian Weissinger; Jan Schleicher; Gerlinde Egerer; Antje Haas; Rebekka Schirren; Jörg Beyer; Carsten Bokemeyer; Oliver Rick
Journal:  J Clin Oncol       Date:  2007-07-01       Impact factor: 44.544

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  34 in total

1.  Salvage chemotherapy for metastatic germ cell tumours: The known unknowns.

Authors:  Aaron R Hansen; Philippe L Bedard
Journal:  Can Urol Assoc J       Date:  2012-04       Impact factor: 1.862

2.  Urologic oncology: Poor trial accrual hinders germ cell tumor therapy advances.

Authors:  Michael V Williams; Danish Mazhar
Journal:  Nat Rev Urol       Date:  2012-04-03       Impact factor: 14.432

3.  [Update on first-line and relapse chemotherapy for testicular cancer].

Authors:  A Lorch; P Albers
Journal:  Urologe A       Date:  2013-11       Impact factor: 0.639

Review 4.  High-dose chemotherapy and stem cell transplantation for advanced testicular cancer.

Authors:  Martin H Voss; Darren R Feldman; Robert J Motzer
Journal:  Expert Rev Anticancer Ther       Date:  2011-07       Impact factor: 4.512

Review 5.  Transplantation for refractory germ cell tumors: does it really make a difference?

Authors:  Yago Nieto
Journal:  Curr Oncol Rep       Date:  2013-06       Impact factor: 5.075

6.  Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review.

Authors:  Irbaz Bin Riaz; Muhammad Umar; Umar Zahid; Muhammad Husnain; Ahmad Iftikhar; Ali McBride; Jawad Bilal; Asad Javed; Sara Akbar; Parminder Singh; Zeeshan Ali; Qurat Ul Ain Riaz Sipra; Farva Razia Gondal; Frederick Ahman; Faiz Anwer
Journal:  Bone Marrow Transplant       Date:  2018-04-27       Impact factor: 5.483

7.  Chemotherapy intensification for first-line treatment of poor-prognosis metastatic germ cell cancer is not yet ready for prime time.

Authors:  Di Maria Jiang; Robert J Hamilton; Aaron R Hansen
Journal:  Can Urol Assoc J       Date:  2020-02       Impact factor: 1.862

Review 8.  Primary intracranial germ-cell tumors in adults: a practical review.

Authors:  Jacoline E C Bromberg; Brigitta G Baumert; Filip de Vos; Johanna M M Gijtenbeek; Erkan Kurt; Anneke M Westermann; Pieter Wesseling
Journal:  J Neurooncol       Date:  2013-03-23       Impact factor: 4.130

Review 9.  [Management of chemotherapy side effects and their long-term sequelae].

Authors:  Isabella M Zraik; Yasmine Heß-Busch
Journal:  Urologe A       Date:  2021-06-29       Impact factor: 0.639

Review 10.  High dose chemotherapy with stem cell support in the treatment of testicular cancer.

Authors:  Lazar Popovic; Gorana Matovina-Brko; Milica Popovic; Dragana Petrovic; Ana Cvetanovic; Jelena Vukojevic; Darjana Jovanovic
Journal:  World J Stem Cells       Date:  2015-12-26       Impact factor: 5.326

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