Testicular cancer
Page editor | Section editor | ||
---|---|---|---|
Michael J. Glover, MD Stanford University Palo Alto, CA, USA |
Ali Raza Khaki, MD Stanford University Palo Alto, CA, USA |
Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: Except for primary treatment for stage I seminoma, these regimens are generally applicable to seminoma and non-seminoma histologies.
Last updated on 2024-12-02: 26 regimens on this page
37 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
AUA
- 2024: Stephenson et al. Diagnosis and Treatment of Early-Stage Testicular Cancer: AUA Guideline Amendment 2023. PubMed
ESMO
- 2018: Honecker et al. [hhttps://doi.org/10.1093/annonc/mdy217 ESMO Consensus Conference Guidelines on testicular germ cell cancer: diagnosis, treatment and follow-up] PubMed
- 2013: Oldenburg et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Schmoll et al. Testicular seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Schmoll et al. Testicular seminoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Huddart. Testicular seminoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Huddart & Kataja. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of testicular seminoma PubMed
- 2001: ESMO minimum clinical recommendations for diagnosis, treatment and follow-up of testicular seminoma PubMed
- 2010: Schmoll et al. Testicular non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
ESMO-EURACAN
NCCN
- NCCN Guidelines - Testicular Cancer
- 2015: Motzer et al. Testicular Cancer, Version 2.2015 PubMed
- 2009: Motzer et al. NCCN clinical practice guidelines in oncology: testicular cancer. PubMed
Adjuvant therapy for resectable disease
BEP
BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Albers et al. 2008 (AUO AH 01/94) | 1996-2005 | Phase 3 (E-switch-ooc) | RPLND | Superior RFS (secondary endpoint) |
Preceding treatment
Chemotherapy
- Bleomycin (Blenoxane) 30 units IV bolus once per day on days 1, 8, 15
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
15-day course
References
- AUO AH 01/94: Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Weissbach L, Loy V, Wittekind C, Hartmann M; German Testicular Cancer Study Group. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol. 2008 Jun 20;26(18):2966-72. Epub 2008 May 5. Erratum in: J Clin Oncol. 2010 Mar 10;28(8):1439. Dosage error in article text. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Hiester A, Fingerhut A, Niegisch G, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Loy V, Wittekind C, Hartmann M, Albers P. Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection - A 13-year follow-up analysis of a phase III trial cohort. Eur J Cancer. 2021 Sep;155:64-72. Epub 2021 Aug 6. link to original article PubMed
Carboplatin monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oliver et al. 2005 (MRC TE19/EORTC 30982) | 1996-2001 | Phase 3 (E-switch-ooc) | Radiation therapy | Seems to have non-inferior RFS (secondary endpoint) |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 7 IV once on day 1
- AUC 7 was described in Oliver et al. 2005 & Oliver et al. 2011 as [7 x (GFR + 25)] mg. eGFR was calculated by EDTA; if CrCl via 24-hour urine collection was used, 90% of the [7 x (GFR + 25)] mg dose was used. The Calvert formula for carboplatin dosing is: Dose (mg) = (target AUC) x (GFR + 25).
One dose
Regimen variant #2, 2 doses carboplatin
Study | Dates of enrollment | Evidence |
---|---|---|
Aparicio et al. 2005 (Second Spanish Germ Cell Cancer Group study) | 1999-01 to 2003-12 | Non-randomized |
Aparicio et al. 2011 (Third Spanish Germ Cell Cancer Group study) | 2004-2008 | Non-randomized |
Patients with stage I seminoma and local risk factors:
- Tumor greater than 4 cm
- Rete testis invasion
Patients in Aparicio et al. 2005 had at least one risk factor; patients in Aparicio et al. 2011 had at both risk factors.
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 7 IV once on day 1
Supportive therapy
21-day cycle for 2 cycles
References
- MRC TE19/EORTC 30982: Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC; EORTC. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003014
- Update: Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, Gabe R, Pollock P, Stenning SP. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study. J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Second Spanish Germ Cell Cancer Group study: Aparicio J, Germà JR, García del Muro X, Maroto P, Arranz JA, Sáenz A, Barnadas A, Dorca J, Gumà J, Olmos D, Bastús R, Carles J, Almenar D, Sánchez M, Paz-Ares L, Satrústegui JJ, Mellado B, Balil A, López-Brea M, Sánchez A; Spanish Germ Cell Cancer Cooperative Group. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol. 2005 Dec 1;23(34):8717-23. Epub 2005 Oct 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Third Spanish Germ Cell Cancer Group study: Aparicio J, Maroto P, del Muro XG, Gumà J, Sánchez-Muñoz A, Margelí M, Doménech M, Bastús R, Fernández A, López-Brea M, Terrassa J, Meana A, del Prado PM, Sastre J, Satrústegui JJ, Gironés R, Robert L, Germà JR; Spanish Germ Cell Cancer Cooperative Group. Risk-adapted treatment in clinical stage I testicular seminoma: the third Spanish Germ Cell Cancer Group study. J Clin Oncol. 2011 Dec 10;29(35):4677-81. Epub 2011 Oct 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Radiation therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jones et al. 2005 (MRC TE18/EORTC 30942) | 1995-1998 | Phase 3 (C) | RT; lower-dose | Did not meet primary endpoint of RFS24 |
Oliver et al. 2005 (MRC TE19/EORTC 30982) | 1996-2001 | Phase 3 (C) | Carboplatin | Seems to have non-inferior RFS |
Note: radiation details are available in the references.
Preceding treatment
Radiotherapy
- External beam radiotherapy 3000 cGy (see note)
References
- MRC TE18/EORTC 30942: Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, Stenning SP; MRC; EORTC. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I testicular seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol. 2005 Feb 20;23(6):1200-8. link to original article PubMed
- MRC TE19/EORTC 30982: Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP; MRC; EORTC. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29;366(9482):293-300. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003014
- Update: Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, Gabe R, Pollock P, Stenning SP. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study. J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Upfront therapy for disseminated disease
BEP
BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PVP16B: Platinol (Cisplatin), VP-16 (Etoposide), Bleomycin
Regimen variant #1, 90/500/100 x 3 ("standard" BEP)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Einhorn et al. 1989 | 1984-1987 | Phase 3 (E-de-esc) | BEP x 4 | Seems to have equivalent DFS |
Toner et al. 2001 | 1994-2000 | Phase 3 (C) | Modified BEP; 30/360/100 | Seems to have superior OS1 |
de Wit et al. 2001 | 1995-1998 | Phase 3 (E-de-esc) | 1. BEP x 4 | Equivalent PFS |
2. BEP; 3-day etoposide x 3 3. BEP; 3-day etoposide x 4 |
Equivalent PFS |
1Reported efficacy for Toner et al. 2001 is based on the 2010 update.
Chemotherapy
- Bleomycin (Blenoxane) 30 units IV bolus once per day on days 1, 8, 15
- Etoposide (Vepesid) 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 5
21-day cycle for 3 cycles
Regimen variant #2, 90/500/100 x 4 ("standard" BEP)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Williams et al. 1987a | 1982-1984 | Phase 3 (E-switch-ic) | BVP | Did not meet primary endpoint of OS1 |
Einhorn et al. 1989 | 1984-1987 | Phase 3 (C) | BEP x 3 | Seems to have equivalent DFS |
Nichols et al. 1998 (ECOG E3887) | 1987-1992 | Phase 3 (C) | VIP | Did not meet efficacy endpoints |
de Wit et al. 2001 | 1995-1998 | Phase 3 (C) | 1. BEP x 3 | Equivalent PFS |
2. BEP; 3-day etoposide x 3 3. BEP; 3-day etoposide x 4 |
Equivalent PFS | |||
Culine et al. 2008 (T93MP) | 1994-2000 | Phase 3 (C) | CISCA/VB | Did not meet primary endpoint of FRR |
Motzer et al. 2007 (SWOG-9442) | 1994-2003 | Phase 3 (C) | BEP x 2, then HDCT x 2 | Did not meet primary endpoint of durable CR at 12 mo |
de Wit et al. 2012 (EORTC 30983) | 1998-2009 | Phase 3 (C) | T-BEP | Seems to have inferior PFS36 |
Daugaard et al. 2010 (EORTC 30974) | 1999-2007 | Phase 3 (C) | BEP x 1, then HDCT x 3 | Might have inferior FFS |
Fizazi et al. 2014 (GETUG 13) | 2003-2012 | Risk-adapted therapy |
1There seemed to be a survival advantage in the high tumor volume subgroup, but no difference was seen in the overall group.
Note: this was the favorable decline rate subset of GETUG 13.
Chemotherapy
- Bleomycin (Blenoxane) 30 units IV bolus once per day on days 1, 8, 15
- Note: Williams et al. 1987 gave bleomycin on days 2, 9, 16
- Note: de Wit et al. 2001 only used bleomycin for cycles 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV over 15 to 60 minutes once per day on days 1 to 5
Supportive therapy
- (as described in Nichols et al. 1998):
- Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, given prior to cisplatin
- Normal saline 100 mL/hour IV throughout the 5 day course of cisplatin, ending 6 hours after each cycle's last cisplatin dose
- G-CSF (type not specified) 5 mcg/kg SC once per day on days 7, 9 to 14, 16, 17
21-day cycle for 4 cycles
Regimen variant #3, 90/495/100 x 3 (3-day etoposide)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Wit et al. 2001 | 1995-1998 | Phase 3 (E-de-esc) | 1. BEP x 3 2. BEP x 4 |
Equivalent PFS |
3. BEP; 3-day etoposide x 4 | Equivalent PFS |
Chemotherapy
- Bleomycin (Blenoxane) 30 units IV once per day on days 1, 8, 15
- Etoposide (Vepesid) 165 mg/m2 IV once per day on days 1 to 3
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1 to 2
21-day cycle for 3 cycles
Regimen variant #4, 90/495/100 x 4 (3-day etoposide)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Wit et al. 2001 | 1995-1998 | Phase 3 (E-esc) | 1. BEP x 3 2. BEP x 4 |
Equivalent PFS |
3. BEP; 3-day etoposide x 3 | Equivalent PFS |
Chemotherapy
- Bleomycin (Blenoxane) as follows:
- Cycles 1 to 3: 30 units IV once per day on days 1, 8, 15
- Etoposide (Vepesid) 165 mg/m2 IV once per day on days 1 to 3
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1 to 2
21-day cycle for 4 cycles
Regimen variant #5, 45/500/100 (modified BEP)
Study | Evidence |
---|---|
Fosså et al. 2005 (EORTC 30948) | Phase 2 |
Note that the dose of bleomycin is lower than standard BEP.
Chemotherapy
- Bleomycin (Blenoxane) 15 mg IV once per day on days 1, 8, 15
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
21-day cycle for 3 cycles
References
- Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987 Jun 4;316(23):1435-40. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Einhorn LH, Williams SD, Loehrer PJ, Birch R, Drasga R, Omura G, Greco FA; Southeastern Cancer Study Group. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989 Mar;7(3):387-91. link to original article PubMed
- Update: Saxman SB, Finch D, Gonin R, Einhorn LH. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indiana University experience. J Clin Oncol. 1998 Feb;16(2):702-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E3887: Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr;16(4):1287-93. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
- Update: Hinton S, Catalano PJ, Einhorn LH, Nichols CR, Crawford ED, Vogelzang N, Trump D, Loehrer PJ Sr. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003 Apr 15;97(8):1869-75. link to original article PubMed
- Toner GC, Stockler MR, Boyer MJ, Jones M, Thomson DB, Harvey VJ, Olver IN, Dhillon H, McMullen A, Gebski VJ, Levi JA, Simes RJ; Australian and New Zealand Germ Cell Trial Group. Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Lancet. 2001 Mar 10;357(9258):739-45. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Grimison PS, Stockler MR, Thomson DB, Olver IN, Harvey VJ, Gebski VJ, Lewis CR, Levi JA, Boyer MJ, Gurney H, Craft P, Boland AL, Simes RJ, Toner GC. Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial. J Natl Cancer Inst. 2010 Aug 18;102(16):1253-62. Epub 2010 Jul 14. link to original article PubMed
- de Wit R, Roberts JT, Wilkinson PM, de Mulder PH, Mead GM, Fosså SD, Cook P, de Prijck L, Stenning S, Collette L; European Organisation for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group; MRC. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organisation for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol. 2001 Mar 15;19(6):1629-40. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 30948: Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- SWOG-9442: Motzer RJ, Nichols CJ, Margolin KA, Bacik J, Richardson PG, Vogelzang NJ, Bajorin DF, Lara PN Jr, Einhorn L, Mazumdar M, Bosl GJ. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol. 2007 Jan 20;25(3):247-56. link to original article refers to Williams et al. 1998 PubMed NCT00002596
- T93MP: Culine S, Kramar A, Théodore C, Geoffrois L, Chevreau C, Biron P, Nguyen BB, Héron JF, Kerbrat P, Caty A, Delva R, Fargeot P, Fizazi K, Bouzy J, Droz JP; Genito-Urinary Group of the French Federation of Cancer Centers. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol. 2008 Jan 20;26(3):421-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 30974: Daugaard G, Skoneczna I, Aass N, De Wit R, De Santis M, Dumez H, Marreaud S, Collette L, Lluch JR, Bokemeyer C, Schmoll HJ. 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). Ann Oncol. 2011 May;22(5):1054-61. Epub 2010 Nov 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00003941
- EORTC 30983: de Wit R, Skoneczna I, Daugaard G, De Santis M, Garin A, Aass N, Witjes AJ, Albers P, White JD, Germa-Lluch JR, Marreaud S, Collette L. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983. J Clin Oncol. 2012 Mar 10;30(8):792-9. Epub 2012 Jan 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00003643
- GETUG 13: Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L, Kerbrat P, Chevreau C, Delva R, Rolland F, Theodore C, Roubaud G, Gravis G, Eymard JC, Malhaire JP, Linassier C, Habibian M, Martin AL, Journeau F, Reckova M, Logothetis C, Culine S. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014 Dec;15(13):1442-50. Epub 2014 Nov 13. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00104676
- Update: Fizazi K, Le Teuff G, Fléchon A, Pagliaro L, Mardiak J, Geoffrois L, Laguerre B, Chevreau C, Delva R, Rolland F, Theodore C, Roubaud G, Gravis G, Eymard JC, Cancel M, Juzyna B, Reckova M, Naoun N, Logothetis C, Culine S. Personalized Chemotherapy on the Basis of Tumor Marker Decline in Poor-Prognosis Germ-Cell Tumors: Updated Analysis of the GETUG-13 Phase III Trial. J Clin Oncol. 2024 Oct;42(28):3270-3276. Epub 2024 Aug 21. link to original article PubMed
Accelerated BEP
Accelerated BEP: Accelerated Bleomycin, Etoposide, Platinol (Cisplatin)
Regimen variant #1, good prognosis
Study | Dates of enrollment | Evidence |
---|---|---|
Grimison et al. 2014 | 2008-2010 | Phase 2 |
Chemotherapy
- Bleomycin (Blenoxane) as follows:
- Cycles 1 to 4: 30 mg IV once per day on days 1 & 8
- Cycle 5: 30 mg IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 3: 100 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) as follows:
- Cycles 1 to 3: 20 mg/m2 IV once per day on days 1 to 5
Supportive therapy
- Pegfilgrastim (Neulasta) as follows:
- Cycles 1 to 3: 6 mg SC once on day 6
14-day cycle for 5 cycles
Regimen variant #2, intermediate or poor prognosis
Study | Dates of enrollment | Evidence |
---|---|---|
Grimison et al. 2014 | 2008-2010 | Phase 2 |
Chemotherapy
- Bleomycin (Blenoxane) 30 mg IV once per day on days 1 & 8
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 20 mg/m2 IV once per day on days 1 to 5
Supportive therapy
- Pegfilgrastim (Neulasta) as follows:
- Cycles 1 to 4: 6 mg SC once on day 6
14-day cycle for 6 cycles
References
- Grimison PS, Stockler MR, Chatfield M, Thomson DB, Gebski V, Friedlander M, Boland AL, Houghton B, Gurney H, Rosenthal M, Singhal N, Kichenadasse G, Wong SS, Lewis CR, Vasey PA, Toner GC; Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Ann Oncol. 2014 Jan;25(1):143-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed ACTRN 12607000294459
Bleomycin & Vincristine (BO)
BO: Bleomycin & Oncovin (Vincristine)
Regimen
Study | Evidence |
---|---|
Fosså et al. 2005 (EORTC 30948) | Phase 2 |
Preceding treatment
- C-BOP x 2
Chemotherapy
- Bleomycin (Blenoxane) 15 mg IV once per day on days 1 & 8
- Vincristine (Oncovin) 2 mg IV once per day on days 1 & 8
14-day course
Subsequent treatment
- BEP; modified x 3
References
- EORTC 30948: Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
C-BOP
C-BOP: Cisplatin, Bleomycin, Oncovin (Vincristine), Paraplatin (Carboplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fosså et al. 2005 (EORTC 30948) | 1996-1998 | Phase 2 | ||
Huddart et al. 2014 (MRC TE23) | 2005-2009 | Randomized Phase 2 (E-esc) | BEP | Seems to have superior FRR (primary endpoint) |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1 & 2, then 40 mg/m2 IV once on day 8
- Vincristine (Oncovin) 2 mg IV once per day on days 1 & 8
- Bleomycin (Blenoxane) 15 mg IV once per day on days 1 & 8, then 15 mg/day IV continuous infusion over 120 hours, started on day 8 (total dose per cycle: 105 mg)
- Carboplatin (Paraplatin) AUC 3 IV once on day 8
14-day cycle for 2 cycles
References
- EORTC 30948: Fosså SD, Paluchowska B, Horwich A, Kaiser G, de Mulder PH, Koriakine O, van Oosterom AT, de Prijck L, Collette L, de Wit R; EORTC GU Group. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer. 2005 Nov 28;93(11):1209-14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- MRC TE23: Huddart RA, Gabe R, Cafferty FH, Pollock P, White JD, Shamash J, Cullen MH, Stenning SP; TE23 Trial Management Group and Collaborators; National Cancer Research Institute Testis Cancer Clinical Studies Group. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604). Eur Urol. 2015 Mar;67(3):534-43. Epub 2014 Jul 4. link to original article link to PMC article PubMed ISRCTN53643604
Cisplatin & Etoposide (EP)
EP: Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bosl et al. 1988 | 1982-1986 | Phase 3 (E-de-esc) | VAB-6 | Did not meet efficacy endpoints |
Bajorin et al. 1993 | 1986-1990 | Phase 3 (C) | CE | Seems to have superior EFS |
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 cycles
References
- Bosl GJ, Geller NL, Bajorin D, Leitner SP, Yagoda A, Golbey RB, Scher H, Vogelzang NJ, Auman J, Carey R, Fair WR, Herr H, Morse M, Sogani P, Whitmore W. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol. 1988 Aug;6(8):1231-8. link to original article PubMed
- Update: Xiao H, Mazumdar M, Bajorin DF, Sarosdy M, Vlamis V, Spicer J, Ferrara J, Bosl GJ, Motzer RJ. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997 Jul;15(7):2553-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Bajorin DF, Sarosdy MF, Pfister DG, Mazumdar M, Motzer RJ, Scher HI, Geller NL, Fair WR, Herr H, Sogani P, Sheinfeld J, Russo P, Vlamis V, Carey R, Vogelzang NJ, Crawford ED, Bosl GJ. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol. 1993 Apr;11(4):598-606. link to original article PubMed
- Update: Xiao H, Mazumdar M, Bajorin DF, Sarosdy M, Vlamis V, Spicer J, Ferrara J, Bosl GJ, Motzer RJ. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997 Jul;15(7):2553-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Kondagunta GV, Bacik J, Bajorin D, Dobrzynski D, Sheinfeld J, Motzer RJ, Bosl GJ. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol. 2005 Dec 20;23(36):9290-4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
M-TIP
M-TIP: Methotrexate, Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Pectasides et al. 2008a | 1997-07 to 2003-11 | Phase 2 |
Chemotherapy
- Methotrexate (MTX) 250 mg/m2 IV over 4 hours once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- Ifosfamide (Ifex) 1200 mg/m2 IV over 120 minutes once per day on days 2 to 6
- Cisplatin (Platinol) 20 mg/m2 IV over 120 minutes once per day on days 2 to 6
Supportive therapy
- Leucovorin (Folinic acid) 15 mg (route not specified) four doses, given 24, 36, 48, and 60 hours after start of methotrexate
- Mesna (Mesnex) 400 mg/m2 IV three times per day on days 2 to 6, given before ifosfamide and then every 4 hours
- Dexamethasone (Decadron) 20 mg (route not specified) twice per day, given 12 and 6 hours before paclitaxel
- Ranitidine (Zantac) 50 mg IV once on day 1, given 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg PO once on day 1, given 30 minutes prior to paclitaxel
- G-CSF SC once per day on days 6 to 14
21-day cycle for 4 cycles
References
- Pectasides D, Pectasides E, Papaxoinis G, Xiros N, Kamposioras K, Tountas N, Economopoulos T. Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors. Urol Oncol. 2010 Nov-Dec;28(6):617-23. Epub 2008 Dec 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed
PVeBV
PVeBV: Platinol (Cisplatin), Velban (Vinblastine), Bleomycin, Vepesid (Etoposide)
VBEP: Vinblastine, Bleomycin, Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chevreau et al. 1993 | Not reported in abstract | Phase 3 (C) | PVeBV-PEC | Did not meet efficacy endpoints of CR rate/OS |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV once per day on days 1 to 5
- Vinblastine (Velban) 0.2 mg/kg IV once on day 1
- Bleomycin (Blenoxane) 30 mg IV once per day on days 1, 8, 15
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
21-day cycle for 3 to 4 cycles
References
- Chevreau C, Droz JP, Pico JL, Biron P, Kerbrat P, Cure H, Héron JF, Chevallier B, Fargeot P, Kramar A, Bouzy J. Early intensified chemotherapy with autologous bone marrow transplantation in first line treatment of poor risk non-seminomatous germ cell tumours: preliminary results of a French randomized trial. Eur Urol. 1993;23(1):213-7. link to original article PubMed
- Update: Droz JP, Kramar A, Biron P, Pico JL, Kerbrat P, Pény J, Curé H, Chevreau C, Théodore C, Bouzy J, Culine S; Genito-Urinary Group of the French Federation of Cancer Centers. Failure of high-dose cyclophosphamide and etoposide combined with double-dose cisplatin and bone marrow support in patients with high-volume metastatic nonseminomatous germ-cell tumours: mature results of a randomised trial. Eur Urol. 2007 Mar;51(3):739-46. Epub 2006 Oct 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
VIP
VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nichols et al. 1998 (ECOG E3887) | 1987-1992 | Phase 3 (E-switch-ic) | BEP | Did not meet efficacy endpoints |
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 5
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
Supportive therapy
- Mesna (Mesnex) 120 mg/m2 IV slow push once on day 1 given prior to ifosfamide, then 1200 mg/m2/day IV continuous infusion over 120 hours (though not clearly specified in Nichols et al. 1998, based on its use with ifosfamide, it is assumed that the mesna dose was 1200 mg/m2/day)
- Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, prior to cisplatin
- Normal saline 100 mL/hour IV throughout the 5 day course of cisplatin, ending 6 hours after each cycle's last cisplatin dose
- G-CSF (type not specified) 5 mcg/kg SC once per day on days 7 to 16
21-day cycle for 4 cycles
References
- ECOG E3887: Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998 Apr;16(4):1287-93. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Hinton S, Catalano PJ, Einhorn LH, Nichols CR, David Crawford E, Vogelzang N, Trump D, Loehrer PJ Sr. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003 Apr 15;97(8):1869-75. link to original article PubMed
Relapsed or refractory, salvage therapy
Carboplatin & Etoposide (CE), then auto HSCT
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Nichols et al. 1989 | 1986-09 to 1988-03 | Phase 1/2 |
Einhorn et al. 2007a | 1996-02 to 2004-12 | Retrospective |
Note: the doses here are the ones from the retrospective NEJM article, not from the prospective phase I/II trial. Some patients had salvage VeIP prior to high-dose therapy; others proceeded directly with this regimen as their first salvage treatment.
Chemotherapy
- Carboplatin (Paraplatin) 700 mg/m2 IV once per day on days -5, -4, -3
- Etoposide (Vepesid) 750 mg/m2 IV once per day on days -5, -4, -3
- At least 1 million CD34+ cells per kilogram of body weight was needed for each cycle of chemotherapy.
2 cycles, with the second cycle starting after "recovery of granulocyte and platelet counts"
Subsequent treatment
- "Most patients" who had CR/PR after two cycles of therapy received etoposide consolidation
References
- Nichols CR, Tricot G, Williams SD, van Besien K, Loehrer PJ, Roth BJ, Akard L, Hoffman R, Goulet R, Wolff SN, Giannone L, Greer J, Einhorn LH, Jansen J. Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989 Jul;7(7):932-9. link to original article PubMed
- Retrospective: Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007 Jul 26;357(4):340-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin & Epirubicin
CIS-EPI: CISplatin, EPIrubicin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Bedano et al. 2006 | 2001-03 to 2005-08 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
- Epirubicin (Ellence) 90 mg/m2 IV over 15 to 30 minutes once on day 1
Supportive therapy
- WBC support with ONE of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 7 to 16
- Pegfilgrastim (Neulasta) 6 mg SC once on either day 6 or 7
21-day cycle for up to 4 cycles
References
- Bedano PM, Brames MJ, Williams SD, Juliar BE, Einhorn LH. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol. 2006 Dec 1;24(34):5403-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
GIP
GIP: Gemcitabine, Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fizazi et al. 2014 (GIP-TG) | 2004-2009 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 5
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
Supportive therapy
- Mesna (Mesnex) 500 mg/m2 IV four times per day on days 1 to 5, given at hours 0, 3, 7, and 11 of each day
- Lenograstim (Granocyte) 263 mcg SC once per day on days 7 to 14
21-day cycle for 4 cycles
References
- GIP-TG: Fizazi K, Gravis G, Flechon A, Geoffrois L, Chevreau C, Laguerre B, Delva R, Eymard JC, Rolland F, Houede N, Laplanche A, Burcoveanu D, Culine S. Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial. Ann Oncol. 2014 May;25(5):987-91. Epub 2014 Mar 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00127049
Ifosfamide & Paclitaxel
TI: Taxol (Paclitaxel) & Ifosfamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kondagunta et al. 2007 | 1998-01 to 2003-05 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Ifosfamide (Ifex) 2000 mg/m2 IV over 4 hours once per day on days 2 to 4, with mesna
Supportive therapy
- Mesna (Mesnex) with ifosfamide on days 2 to 4 (no further details given)
14-day cycle for 2 cycles; leukapheresis on days 11 to 13 (done on cycle 1, and then only if needed on cycle 2 to have at least 6 x 106 CD34+ cells/kg body weight in peripheral blood stem cells)
Subsequent treatment
References
- Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. Erratum in: J Clin Oncol. 2007 May 20;25(15):2149. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Feldman DR, Sheinfeld J, Bajorin DF, Fischer P, Turkula S, Ishill N, Patil S, Bains M, Reich LM, Bosl GJ, Motzer RJ. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010 Apr 1;28(10):1706-13. Epub 2010 Mar 1. Erratum in: J Clin Oncol. 2010 Dec 1;28(34):5126. link to original article link to PMC article PubMed
TIP
TIP: Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)
Regimen variant #1, 175/6000/100
Study | Dates of enrollment | Evidence |
---|---|---|
Kurobe et al. 2014 | 2000-2012 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Ifosfamide (Ifex) 1200 mg/m2 IV over 120 minutes once per day on days 2 to 6
- Cisplatin (Platinol) 20 mg/m2 IV over 120 minutes once per day on days 2 to 6
Supportive therapy
- Mesna (Mesnex) 240 mg/m2 IV three times per day on days 2 to 6, given once prior to each dose of ifosfamide, once 4 hours after each dose of ifosfamide, and once 8 hours after each dose of ifosfamide
21-day cycle for 4 cycles
Regimen variant #2, 250/6000/100
Study | Dates of enrollment | Evidence |
---|---|---|
Kondagunta et al. 2005 | Not reported | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 250 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Ifosfamide (Ifex) 1500 mg/m2 IV over 60 minutes once per day on days 2 to 5
- Cisplatin (Platinol) 25 mg/m2 IV over 30 minutes once per day on days 2 to 5
Supportive therapy
- Mesna (Mesnex) 500 mg/m2 IV three times per day on days 2 to 5, given once prior to each dose of ifosfamide, once 4 hours after each dose of ifosfamide, and once 8 hours after each dose of ifosfamide
- Dexamethasone (Decadron) 20 mg PO twice on day 1, given 14 and 7 hours prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1, given 60 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1, given 60 minutes prior to paclitaxel
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 7 to 18, discontinued if WBC greater than 10 x 109/L for 2 sequential days
21-day cycle for 4 cycles
References
- Kondagunta GV, Bacik J, Donadio A, Bajorin D, Marion S, Sheinfeld J, Bosl GJ, Motzer RJ. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005 Sep 20;23(27):6549-55. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Kurobe M, Kawai K, Oikawa T, Ichioka D, Kandori S, Takaoka E, Kojima T, Joraku A, Suetomi T, Miyazaki J, Nishiyama H. Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and consolidation chemotherapy for advanced germ cell tumor. J Cancer Res Clin Oncol. 2015 Jan;141(1):127-33. Epub 2014 Jul 26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Alliance A031102: NCT02375204
VeIP
VeIP: Velban (Vinblastine), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Loehrer et al. 1988 | 1983-1986 | Phase 2 (RT) |
Loehrer et al. 1998 | 1984-1989 | Phase 2 |
Prior treatment criteria
- Loehrer et al. 1998: Cisplatin & etoposide based combination chemotherapy
Chemotherapy
- Vinblastine (Velban) 0.11 mg/kg IV once per day on days 1 & 2
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV over 60 minutes once per day on days 1 to 5
Supportive therapy
- Mesna (Mesnex) 400 mg/m2 IV bolus on day 1 prior to first dose of ifosfamide, then 1200 mg/m2/day IV continuous infusion over 120 hours (total dose per cycle: 6400 mg/m2)
- Normal saline 100 mL/hour IV continuous infusion over 120 hours, started on day 1
21-day cycle for 4 cycles
References
- Loehrer PJ Sr, Lauer R, Roth BJ, Williams SD, Kalasinski LA, Einhorn LH. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med. 1988 Oct 1;109(7):540-6. link to original article PubMed
- Loehrer PJ Sr, Gonin R, Nichols CR, Weathers T, Einhorn LH. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998 Jul;16(7):2500-4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
VIP
VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
PEI: Platinol (Cisplatin), Etoposide, Ifosfamide
Regimen variant #1, 1 cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lorch et al. 2007 | 1999-2004 | Phase 3 (C) | VIP-CEC | Did not meet primary endpoint of EFS12 |
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 5
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
21-day course
Subsequent treatment
Regimen variant #2, 4 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Loehrer et al. 1986 | 1983-02 to 1984-10 | Non-randomized (RT) | ||
Pico et al. 2005 (IT 94) | 1994-2001 | Phase 3 (C) | VIP-CarboPEC | Did not meet primary endpoint of EFS |
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 5
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 cycles
References
- Loehrer PJ Sr, Einhorn LH, Williams SD. VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer. J Clin Oncol. 1986 Apr;4(4):528-36. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- IT 94: Pico JL, Rosti G, Kramar A, Wandt H, Koza V, Salvioni R, Theodore C, Lelli G, Siegert W, Horwich A, Marangolo M, Linkesch W, Pizzocaro G, Schmoll HJ, Bouzy J, Droz JP, Biron P; Genito-Urinary Group of the French Federation of Cancer Centers; EBMT. A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol. 2005 Jul;16(7):1152-9. Epub 2005 May 31. link to original article PubMed
- Lorch A, Kollmannsberger C, Hartmann JT, Metzner B, Schmidt-Wolf IG, Berdel WE, Weissinger F, Schleicher J, Egerer G, Haas A, Schirren R, Beyer J, Bokemeyer C, Rick O; German Testicular Cancer Study Group. 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. J Clin Oncol. 2007 Jul 1;25(19):2778-84. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Lorch A, Kleinhans A, Kramar A, Kollmannsberger CK, Hartmann JT, Bokemeyer C, Rick O, Beyer J. Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial. J Clin Oncol. 2012 Mar 10;30(8):800-5. Epub 2012 Jan 30. link to original article PubMed
Consolidation after salvage therapy
Carboplatin & Etoposide (CE), then auto HSCT
TI-CE: Taxol (Paclitaxel), Ifosfamide, Carboplatin, Etoposide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kondagunta et al. 2007 | 1998-01 to 2003-05 | Phase 2 |
Preceding treatment
- Salvage TI x 2
Chemotherapy
- Carboplatin (Paraplatin) AUC 7 to 8 IV over 20 to 60 minutes once per day on days 1 to 3
- Etoposide (Vepesid) 400 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- Peripheral blood stem cell support (at least 2 x 106 CD34+ cells/kg body weight per infusion) on day 5, 48 hours after carboplatin & etoposide (stem cells were infused each cycle)
14- to 21-day cycle for 3 cycles
References
- Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. Erratum in: J Clin Oncol. 2007 May 20;25(15):2149. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Etoposide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Nichols et al. 1989 | 1986-09 to 1988-03 | Phase 1/2 |
Einhorn et al. 2007a | 1996-02 to 2004-12 | Retrospective |
Preceding treatment
- CE with auto HSCT consolidation
References
- Nichols CR, Tricot G, Williams SD, van Besien K, Loehrer PJ, Roth BJ, Akard L, Hoffman R, Goulet R, Wolff SN, Giannone L, Greer J, Einhorn LH, Jansen J. Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989 Jul;7(7):932-9. link to original article PubMed
- Retrospective: Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007 Jul 26;357(4):340-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Subsequent lines of therapy
Etoposide monotherapy
Regimen
Study | Evidence |
---|---|
Miller & Einhorn 1990 | Phase 2 |
References
- Miller JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990 Feb;17(1 Suppl 2):36-9. PubMed
GemOx
GemOx: GEMcitabine & OXaliplatin
Regimen variant #1, 2000/130
Study | Dates of enrollment | Evidence |
---|---|---|
Pectasides et al. 2004 | 1999-2002 | Phase 2 |
Kollmannsberger et al. 2004 | 2001-2003 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first on day 1
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1, given second
Supportive therapy
- 5-HT3 antagonists
- For patients who developed flu-like symptoms after gemcitabine: Dexamethasone (Decadron) 2 mg (route not specified) given 3 times on days 1 & 8; 30 minutes prior to gemcitabine, 12 hours after gemcitabine, and 24 hours after gemcitabine
21-day cycle for varying durations: at least 2 cycles (Kollmannsberger et al. 2004); 6 cycles (Pectasides et al. 2004)
Regimen variant #2, 2500/130
Study | Dates of enrollment | Evidence |
---|---|---|
De Giorgi et al. 2006 | 2002-05 to 2005-06 | Phase 2, fewer than 20 pts |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1, given second
Supportive therapy
21-day cycles
References
- Kollmannsberger C, Beyer J, Liersch R, Schoeffski P, Metzner B, Hartmann JT, Rick O, Stengele K, Hohloch K, Spott C, Kanz L, Bokemeyer C; German Testicular Cancer Study Group. 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 Jan 1;22(1):108-14. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pectasides D, Pectasides M, Farmakis D, Aravantinos G, Nikolaou M, Koumpou M, Gaglia A, Kostopoulou V, Mylonakis N, Skarlos D. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol. 2004 Mar;15(3):493-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- De Giorgi U, Rosti G, Aieta M, Testore F, Burattini L, Fornarini G, Naglieri E, Lo Re G, Zumaglini F, Marangolo M. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol. 2006 Nov;50(5):1032-8. Epub 2006 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Gemcitabine, Oxaliplatin, Paclitaxel
GOP: Gemcitabine, Oxaliplatin, Paclitaxel
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Bokemeyer et al. 2007 | 2003-2006 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over greater than 2 hours once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1 & 8
Supportive therapy
- "Antiemetic prophylaxis was left to the decision of the treating physician, but a combination of a 5-HT3 antagonist and dexamethasone was proposed."
- Dexamethasone (Decadron) 20 mg IV once per day on days 1 & 8; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1 & 8; 20 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once per day on days 1 & 8; 20 minutes prior to paclitaxel
21-day cycles; given for 2 cycles beyond the best response, up to a maximum of 8 cycles
References
- Bokemeyer C, Oechsle K, Honecker F, Mayer F, Hartmann JT, Waller CF, Böhlke I, Kollmannsberger C; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol. 2008 Mar;19(3):448-53. Epub 2007 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Gemcitabine & Paclitaxel
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Hinton et al. 2002 (ECOG E9897) | 1999-01-11 to 2000-12-30 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given second
- Paclitaxel (Taxol) 110 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, given first
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1, 8, 15; 60 minutes prior to each dose of paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of paclitaxel
- One of the following H2-blockers:
- Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of paclitaxel
- Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of paclitaxel
28-day cycle for up to 6 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Einhorn et al. 2007b | 1996-02 to 2004-12 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given second
- Paclitaxel (Taxol) 100 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, given first
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1, 8, 15; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15; 30 minutes prior to paclitaxel
- One of the following H2-blockers:
- Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15; 30 minutes prior to paclitaxel
- Growth factors "used only for prolonged granulocytopenia."
28-day cycle for up to 6 cycles
References
- ECOG E9897: Hinton S, Catalano P, Einhorn LH, Loehrer PJ Sr, Kuzel T, Vaughn D, Wilding G. 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 Apr 1;20(7):1859-63. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Einhorn LH, Brames MJ, Juliar B, Williams SD. 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 Feb 10;25(5):513-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Oxaliplatin & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Jain et al. 2014 | 2000-11 to 2011-09 | Phase 2 |
Chemotherapy
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV over 90 minutes once on day 1
14-day cycle for 2 to 14 cycles
References
- Jain A, Brames MJ, Vaughn DJ, Einhorn LH. Phase II clinical trial of oxaliplatin and bevacizumab in refractory germ cell tumors. Am J Clin Oncol. 2014 Oct;37(5):450-3. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Sunitinib monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Feldman et al. 2009 | Not reported | Phase 2, fewer than 20 pts |
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Oechsle et al. 2011 | 2007-2010 | Phase 2 |
References
- Feldman DR, Turkula S, Ginsberg MS, Ishill N, Patil S, Carousso M, Bosl GJ, Motzer RJ. Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors. Invest New Drugs. 2010 Aug;28(4):523-8. Epub 2009 Jun 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Oechsle K, Honecker F, Cheng T, Mayer F, Czaykowski P, Winquist E, Wood L, Fenner M, Glaesener S, Hartmann JT, Chi K, Bokemeyer C, Kollmannsberger C; Canadian Urologic Oncology Group; German Testicular Cancer Study Group. Preclinical and clinical activity of sunitinib in patients with cisplatin-refractory or multiply relapsed germ cell tumors: a Canadian Urologic Oncology Group/German Testicular Cancer Study Group cooperative study. Ann Oncol. 2011 Dec;22(12):2654-60. Epub 2011 Mar 17. link to original article PubMed
Statistics
- Stage I seminoma surveillance relapse - Warde P, Specht L, Horwich A, Oliver T, Panzarella T, Gospodarowicz M, von der Maase H. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002 Nov 15;20(22):4448-52. link to original article PubMed
Patient information
- Testicular Cancer Resource Center - detailed website with information for patients and families about testicular cancer