Maintenance Oral Etoposide After High-Dose Chemotherapy (HDCT) for Patients With Relapsed Metastatic Germ-Cell Tumors (mGCT)

Published:January 17, 2023DOI:



      : HDCT and peripheral-blood stem-cell transplant (PBSCT) can cure up to 60% of pts with relapsed mGCT. Maintenance daily oral etoposide after salvage therapy has demonstrated potential clinical benefit. We now evaluate the potential role of maintenance etoposide versus observation post HDCT+PBSCT in this nonrandomized retrospective analysis.


      : The prospectively maintained Indiana University testicular cancer database was interrogated. Patients with relapsed non-seminoma who completed HDCT+PBSCT and achieved complete serologic remission and hematologic recovery were evaluated. Outcomes of pts who received maintenance etoposide (N = 141) were compared to pts who were observed (N = 242). In this retrospective study, Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Univariable and multivariable cox regression models were used to determine variables associated with PFS. We also performed an additional analysis to compare the survival outcomes in the platinum-refractory patients’ subgroup based on maintenance etoposide treatment.


      : Two-year PFS in the maintenance etoposide vs observation group was 55% vs. 46% (P = .028). Two-year OS was 61% vs 54% (P = .04). A multivariable analysis was performed, including the factors: primary tumor site (testis vs. mediastinum), IGCCCG risk, platinum refractory, HDCT line of therapy (2nd vs ≥3rd), tumor marker amplitude at HDCT initiation, and receipt of maintenance etoposide post HDCT vs. observation. Maintenance etoposide was confirmed as an independent predictor of improved PFS with HR 0.51 [95% CI, 0.37-0.70] (P < .001). Two-year OS and PFS for platinum-refractory patients who received maintenance etoposide vs. observation group were 50.2% vs. 26.1% (P < .0001) and 44.2% vs.. 23.1% (P = .0003), respectively. There was no statistically significant difference in 2-year OS and PFS between the platinum-sensitive patients who received maintenance etoposide and those who were observed.


      : Daily oral etoposide therapy produced encouraging efficacy results in patients with relapsed non-seminoma GCT (NSGCT) who completed HDCT and PBSCT and achieved complete serologic remission and hematologic recovery. Patients with platinum-refractory disease and poor prognostic features are potential candidates for daily maintenance oral etoposide post HDCT. These data have led to an ongoing randomized phase II clinical trial (NCT04804007).


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Nigam M
        • Aschebrook-Kilfoy B
        • Shikanov S
        • et al.
        Increasing incidence of testicular cancer in the United States and Europe between 1992 and 2009.
        World J Urol. 2015; 33: 623-631
      1. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group.
        J Clin Oncol. 1997; 15: 594-603
        • Murphy BR
        • Breeden ES
        • Donohue JP
        • et al.
        Surgical salvage of chemorefractory germ cell tumors.
        J Clin Oncol. 1993; 11: 324-329
        • Adra N
        • Abonour R
        • Althouse SK
        • et al.
        High-dose chemotherapy and autologous peripheral-blood stem-cell transplantation for relapsed metastatic germ cell tumors: the Indiana University Experience.
        J Clin Oncol. 2017; 35: 1096-1102
        • Adra N
        • Einhorn LH.
        Testicular cancer update.
        Clin Adv Hematol Oncol. 2017; 15: 386-396
        • Evans SR
        • Krown SE
        • Testa MA
        • et al.
        Phase II evaluation of low-dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi's sarcoma: an AIDS Clinical Trials Group clinical study.
        J Clin Oncol. 2002; 20: 3236-3241
        • Saphner T
        • Weller EA
        • Tormey DC
        • et al.
        21-day oral etoposide for metastatic breast cancer: a phase II study and review of the literature.
        Am J Clin Oncol. 2000; 23: 258-262
        • Schmitz N
        • Trumper L
        • Ziepert M
        • et al.
        Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group.
        Blood. 2010; 116: 3418-3425
        • Rose PG
        • Blessing JA
        • Mayer AR
        • et al.
        Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study.
        J Clin Oncol. 1998; 16: 405-410
        • Evans WK
        • Shepherd FA
        • Feld R
        • et al.
        VP-16 and cisplatin as first-line therapy for small-cell lung cancer.
        J Clin Oncol. 1985; 3: 1471-1477
        • Cooper MA
        • Einhorn LH.
        Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors.
        J Clin Oncol. 1995; 13: 1167-1169
        • Slevin ML
        • Clark PI
        • Joel SP
        • et al.
        A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.
        J Clin Oncol. 1989; 7: 1333-1340
        • Miller JC
        • Einhorn LH.
        Phase II study of daily oral etoposide in refractory germ cell tumors.
        Semin Oncol. 1990; 17: 36-39
        • Albany C
        • Adra N
        • Snavely AC
        • et al.
        Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors.
        Ann Oncol. 2018; 29: 341-346
        • Einhorn LH
        • Williams SD
        • Chamness A
        • et al.
        High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors.
        N Engl J Med. 2007; 357: 340-348
        • Feldman DR
        • Sheinfeld J
        • Bajorin DF
        • et al.
        TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis.
        J Clin Oncol. 2010; 28: 1706-1713
        • Hinton S
        • Catalano P
        • Einhorn LH
        • et al.
        Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group.
        J Clin Oncol. 2002; 20: 1859-1863
        • Einhorn LH
        • Brames MJ
        • Juliar B
        • et al.
        Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant.
        J Clin Oncol. 2007; 25: 513-516
        • Kollmannsberger C
        • Beyer J
        • Liersch R
        • et al.
        Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group.
        J Clin Oncol. 2004; 22: 108-114
        • Pectasides D
        • Pectasides M
        • Farmakis D
        • et al.
        Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study.
        Ann Oncol. 2004; 15: 493-497
        • Adra N
        • Einhorn LH
        • Althouse SK
        • et al.
        Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206.
        Ann Oncol. 2018; 29: 209-214
        • Einhorn LH
        • Brames MJ
        • Heinrich MC
        • et al.
        Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT.
        Am J Clin Oncol. 2006; 29: 12-13
        • Feldman DR
        • Turkula S
        • Ginsberg MS
        • et al.
        Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors.
        Invest New Drugs. 2010; 28: 523-528
        • Jain A
        • Brames MJ
        • Vaughn DJ
        • et al.
        Phase II clinical trial of oxaliplatin and bevacizumab in refractory germ cell tumors.
        Am J Clin Oncol. 2014; 37: 450-453