Testicular cancer

Section editor
	Ali Raza Khaki, MD University of Washington Seattle, WA arkhaki

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. 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.

24 regimens on this page 34 variants on this page

Guidelines

ESMO

• 2018: Honecker et al. ESMO Consensus Conference Guidelines on testicular germ cell cancer: diagnosis, treatment and follow-up

Older

• 2013: Oldenburg et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed

NCCN

• NCCN Guidelines - Testicular Cancer

Adjuvant therapy for resectable disease

BEP

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BEP: Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Albers et al. 2008 (AUO AH 01/94)	1996-2005	Phase III (E-switch-ooc)	RPLND	Superior RFS

Preceding treatment

• Orchiectomy

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

1. 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 contains verified protocol PubMed

Carboplatin monotherapy

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Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Oliver et al. 2005 (MRC TE19/EORTC 30982)	1996-2001	Phase III (E-switch-ooc)	Radiation therapy	Seems to have non-inferior RFS

Preceding treatment

• Orchiectomy

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	Evidence
Aparicio et al. 2005 (Second Spanish Germ Cell Cancer Group study)	Non-randomized
Aparicio et al. 2011 (Third Spanish Germ Cell Cancer Group study)	Non-randomized

Patients with stage I seminoma and local risk factors:

1. Tumor greater than 4 cm
2. 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

• Orchiectomy

Chemotherapy

• Carboplatin (Paraplatin) AUC 7 IV once on day 1

Supportive medications

• Dexamethasone (Decadron)
• 5-hydroxytryptamine-3 (5-HT3) antagonists

21-day cycle for 2 cycles

References

1. 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 contains verified protocol PubMed ISRCTN27163214
   1. 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 (ISRCTN27163214). J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. link to original article contains verified protocol PubMed
2. 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 contains verified protocol PubMed
3. 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 contains verified protocol PubMed

Radiation therapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Jones et al. 2005 (MRC TE18/EORTC 30942)	1995-1998	Phase III (C)	RT; lower-dose	Did not meet primary endpoint of RFS24
Oliver et al. 2005 (MRC TE19/EORTC 30982)	1996-2001	Phase III (C)	Carboplatin	Seems to have non-inferior RFS

Note: radiation details are available in the references.

Preceding treatment

• Orchiectomy

Radiotherapy

• External beam radiotherapy 30 Gy (see note)

References

1. 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
2. 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 contains verified protocol PubMed ISRCTN27163214
   1. 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 (ISRCTN27163214). J Clin Oncol. 2011 Mar 10;29(8):957-62. Epub 2011 Jan 31. link to original article contains verified protocol PubMed

Upfront therapy for disseminated disease

BEP

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BEP: Bleomycin, Etoposide, Platinol (Cisplatin)
PVP16B: Platinol (Cisplatin), VP-16 (Etoposide), Bleomycin

Regimen variant #1, 90/500/100 x 3 ("standard" BEP)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Einhorn et al. 1989	1984-1987	Phase III (E-de-esc)	BEP x 4	Seems to have equivalent DFS
Toner et al. 2001	1994-2000	Phase III (C)	Modified BEP 30/360/100	Seems to have superior OS (*)
de Wit et al. 2001	1995-1998	Phase III (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

Note: reported 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 in 500 mL normal saline 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	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Williams et al. 1987a	1982-1984	Phase III (E-switch-ic)	BVP	Did not meet primary endpoint of OS (*)
Einhorn et al. 1989	1984-1987	Phase III (C)	BEP x 3	Seems to have equivalent DFS
Nichols et al. 1998 (ECOG E3887)	1987-1992	Phase III (C)	VIP	Did not meet efficacy endpoints
de Wit et al. 2001	1995-1998	Phase III (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 III (C)	CISCA/VB	Did not meet primary endpoint of FRR
Motzer et al. 2007	1994-2003	Phase III (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 III (C)	T-BEP	Seems to have inferior PFS36
Daugaard et al. 2010 (EORTC 30974)	1999-2007	Phase III (C)	BEP x 1, then HDCT x 3	Might have inferior FFS
Fizazi et al. 2014 (GETUG 13)	2003-2012	Risk-adapted therapy

Note: this was the favorable decline rate subset of GETUG 13. In Williams et al. 1987, there seemed to be a survival advantage in the high tumor volume subgroup, but no difference was seen in the overall group.

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 in 500 mL normal saline 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 medications

• (as described in Nichols et al. 1998):
• Normal saline 100 mL/hour IV over 12 hours once per day on days 1 to 5, prior to Cisplatin (Platinol)
• Normal saline 100 mL/hour IV throughout the 5 day course of Cisplatin (Platinol), 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	Years of enrollment	Evidence	Comparator	Comparative Efficacy
de Wit et al. 2001	1995-1998	Phase III (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	Years of enrollment	Evidence	Comparator	Comparative Efficacy
de Wit et al. 2001	1995-1998	Phase III (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 II

Note that the dose of bleomycin is lower than standard BEP.

Preceding treatment

• C-BOP x 2, then BO x 1

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

1. 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 contains verified protocol PubMed
2. 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
   1. 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 contains verified protocol PubMed
3. 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 contains verified protocol PubMed content property of HemOnc.org
   1. 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
4. 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 contains protocol PubMed
   1. 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
5. 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 contains verified protocol PubMed
6. 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. contains verified protocol link to PMC article PubMed
7. 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
8. 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 contains verified protocol PubMed
9. 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 contains verified protocol PubMed
10. 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 contains verified protocol link to PMC article PubMed NCT00003643
11. 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 contains verified protocol PubMed NCT00104676

Accelerated BEP

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Accelerated BEP: Accelerated Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence
Grimison et al. 2014	2008-2010	Phase II

Chemotherapy

• Bleomycin (Blenoxane) as follows:
  • Good prognosis: 30,000 IU once per week for 9 doses
  • All others: 30,000 IU once per week for 12 doses
• 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

Supportive medications

• Pegfilgrastim (Neulasta) 6 mg SC once on day 6

14-day cycle for 4 cycles

References

1. 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 contains protocol PubMed ACTRN 12607000294459

BO

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BO: Bleomycin & Oncovin (Vincristine)

Regimen

Study	Evidence
Fosså et al. 2005 (EORTC 30948)	Phase II

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 cycle for 1 cycle

Subsequent treatment

Modified BEP x 3

References

1. 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. contains verified protocol link to PMC article PubMed

C-BOP

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C-BOP: Cisplatin, Bleomycin, Oncovin (Vincristine), Paraplatin (Carboplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fosså et al. 2005 (EORTC 30948)	1996-1998	Phase II
Huddart et al. 2014 (MRC TE23)	2005-2009	Randomized Phase II (E-esc)	BEP	Seems to have superior FRR

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

Subsequent treatment

• BO x 1, then modified BEP x 3

References

1. 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. contains verified protocol link to PMC article PubMed
2. 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

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EP: Etoposide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bosl et al. 1988	1982-1986	Phase III (E-de-esc)	VAB-6	Did not meet efficacy endpoints
Bajorin et al. 1993	1986-1990	Phase III (C)	EC	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

1. 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
   1. 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 contains verified protocol PubMed
2. 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
   1. 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 contains verified protocol PubMed
3. 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 contains verified protocol PubMed

M-TIP

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M-TIP: Methotrexate, Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Evidence
Pectasides et al. 2008a	Phase II

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 medications

• Folinic acid (Leucovorin)

4 cycles

References

1. 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 PubMed

PVeBV

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PVeBV: Platinol (Cisplatin), Velban (Vinblastine), Bleomycin, Vepesid (Etoposide)
VBEP: Vinblastine, Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chevreau et al. 1993	NR in abstract	Phase III (C)	PVeBV, then PEC with auto HSCT	Did not meet efficacy endpoints of CR rate/OS

Chemotherapy

• Cisplatin (Platinol)
• Vinblastine (Velban)
• Bleomycin (Blenoxane)
• Etoposide (Vepesid)

References

1. 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
   1. 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 PubMed

VIP

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VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nichols et al. 1998 (ECOG E3887)	1987-1992	Phase III (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 medications

• Mesna (Mesnex) 120 mg/m² IV slow push once on day 1 given before Ifosfamide (Ifex), 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 (Platinol)
• Normal saline 100 mL/hour IV throughout the 5 day course of Cisplatin (Platinol), 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

1. 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 contains verified protocol PubMed
   1. 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, then auto HSCT

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Regimen

Study	Evidence
Nichols et al. 1989	Phase I/II
Einhorn et al. 2007a	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

1. 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
2. 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 contains verified protocol PubMed

Cisplatin & Epirubicin

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CIS-EPI: CISplatin, EPIrubicin

Regimen

Study	Evidence
Bedano et al. 2006	Phase II

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 medications

• 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

1. 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 contains verified protocol PubMed

GIP

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GIP: Gemcitabine, Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence
Fizazi et al. 2014 (GIP-TG)	2004-2009	Phase II

Chemotherapy

• Gemcitabine (Gemzar)
• Ifosfamide (Ifex)
• Cisplatin (Platinol)

References

1. 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 PubMed NCT00127049

Ifosfamide & Paclitaxel

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TI: Taxol (Paclitaxel) & Ifosfamide

Regimen

Study	Evidence
Kondagunta et al. 2007	Phase II

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

Supportive medications

• Mesna (Mesnex) with Ifosfamide (Ifex) on days 2 to 4 (no further details given)

Stem cell collection

• 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)

14-day cycle for 2 cycles

Subsequent treatment

• Carboplatin & etoposide with auto HSCT

References

1. 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. link to original article contains verified protocol PubMed
   1. 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

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TIP: Taxol (Paclitaxel), Ifosfamide, Platinol (Cisplatin)

Regimen variant #1, 175/6000/100

Study	Evidence
Kurobe et al. 2014	Phase II

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 medications

• Mesna (Mesnex) as follows:
  • 240 mg/m² IV once per day on days 2 to 6, prior to each dose of Ifosfamide (Ifex)
  • 240 mg/m² IV once per day on days 2 to 6; 4 hours after each dose of Ifosfamide (Ifex)
  • 240 mg/m² IV once per day on days 2 to 6; 8 hours after each dose of Ifosfamide (Ifex)

21-day cycle for 4 cycles

Regimen variant #2, 250/6000/100

Study	Evidence
Kondagunta et al. 2005	Phase II

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 medications

• Mesna (Mesnex) as follows:
  • 500 mg/m² IV once per day on days 2 to 5, prior to each dose of Ifosfamide (Ifex)
  • 500 mg/m² IV once per day on days 2 to 5; 4 hours after each dose of Ifosfamide (Ifex)
  • 500 mg/m² IV once per day on days 2 to 5; 8 hours after each dose of Ifosfamide (Ifex)
• Dexamethasone (Decadron) 20 mg PO twice on day 1; 14 and 7 hours prior to Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
• Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
• 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 days

21-day cycle for 4 cycles

References

1. 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 contains verified protocol PubMed
2. 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 contains verified protocol PubMed

VeIP

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VeIP: Velban (Vinblastine), Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence
Loehrer et al. 1988	1983-1986	Phase II (RT)
Loehrer et al. 1998	1984-1989	Phase II

Patients in Loehrer et al. 1998 had previously received 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 medications

• Mesna (Mesnex) 400 mg/m² IV bolus on day 1 prior to first dose of Ifosfamide (Ifex), 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

1. 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
2. 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 contains verified protocol PubMed

VIP

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VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
PEI: Platinol (Cisplatin), Etoposide, Ifosfamide

Regimen variant #1, 1 cycle

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lorch et al. 2007	1999-2004	Phase III (C)	VIP x 3, then CEC with auto HSCT	Did not meet primary endpoint of EFS12

Chemotherapy

• Etoposide (Vepesid)
• Ifosfamide (Ifex)
• Cisplatin (Platinol)

One course

Subsequent treatment

• CE, then auto HSCT x 3

Regimen variant #2, 4 cycles

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pico et al. 2005 (IT 94)	1994-2001	Phase III (C)	VIP x 3, then CarboPEC with auto HSCT	Did not meet primary endpoint of EFS

Chemotherapy

• Etoposide (Vepesid)
• Ifosfamide (Ifex)
• Cisplatin (Platinol)

4 cycles

References

1. 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
2. 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 PubMed
   1. 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, then auto HSCT

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TI-CE: Taxol (Paclitaxel), Ifosfamide, Carboplatin, Etoposide

Regimen

Study	Evidence
Kondagunta et al. 2007	Phase II

Preceding treatment

• 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

Stem cell rescue

• 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

1. 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. link to original article contains verified protocol PubMed

Etoposide monotherapy

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Regimen

Study	Evidence
Nichols et al. 1989	Phase I/II
Einhorn et al. 2007a	Retrospective

Preceding treatment

• Carboplatin & Etoposide with auto HSCT

Chemotherapy

• Etoposide (Vepesid) 50 mg/m² PO once per day on days 1 to 21

28-day cycle for 3 cycles

References

1. 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
2. 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 contains verified protocol PubMed

Subsequent lines of therapy

Etoposide monotherapy

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Regimen

Study	Evidence
Miller & Einhorn 1990	Phase II

Chemotherapy

• Etoposide (Vepesid) 50 mg/m² PO once per day

Continued indefinitely

References

1. 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

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GemOx: GEMcitabine & OXaliplatin

Regimen variant #1, 2000/130

Study	Years of enrollment	Evidence
Pectasides et al. 2004	1999-2002	Phase II
Kollmannsberger et al. 2004	2001-2003	Phase II

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 medications

• 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 (Gemzar), 12 hours after Gemcitabine (Gemzar), and 24 hours after Gemcitabine (Gemzar)

21-day cycle for up to 6 cycles

Regimen variant #2, 2500/130

Study	Evidence
De Giorgi et al. 2006	Phase II, <20 pts

Chemotherapy

• Gemcitabine (Gemzar) 1250 mg/m² IV once per day on days 1 & 8
• Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycles

References

1. 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 PubMed
2. 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 contains verified protocol PubMed
3. 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 contains protocol PubMed

Gemcitabine, Oxaliplatin, Paclitaxel

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GOP: Gemcitabine, Oxaliplatin, Paclitaxel

Regimen

Study	Years of enrollment	Evidence
Bokemeyer et al. 2007	2003-2006	Phase II

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 medications

• "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 (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV once per day on days 1 & 8; 20 minutes prior to Paclitaxel (Taxol)
• Cimetidine (Tagamet) 300 mg IV once per day on days 1 & 8; 20 minutes prior to Paclitaxel (Taxol)

21-day cycles, given for 2 cycles beyond the best response, up to a maximum of 8 cycles

References

1. 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 contains verified protocol PubMed

Gemcitabine & Paclitaxel

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Regimen variant #1

Study	Evidence
Hinton et al. 2002 (ECOG E9897)	Phase II

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 medications

• Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1, 8, 15; 60 minutes prior to each dose of Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of Paclitaxel (Taxol)
• 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 (Taxol)
  • Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15; 60 minutes prior to each dose of Paclitaxel (Taxol)

28-day cycle for up to 6 cycles

Regimen variant #2

Study	Evidence
Einhorn et al. 2007b	Phase II

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 medications

• Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1, 8, 15; 30 minutes prior to Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15; 30 minutes prior to Paclitaxel (Taxol)
• One of the following H2-blockers:
  • Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15; 30 minutes prior to Paclitaxel (Taxol)
  • Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15; 30 minutes prior to Paclitaxel (Taxol)
• Growth factors "used only for prolonged granulocytopenia."

28-day cycle for up to 6 cycles

References

1. 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 contains verified protocol PubMed
2. 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 contains verified protocol PubMed

Oxaliplatin & Bevacizumab

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Regimen

Study	Evidence
Jain et al. 2014	Phase II

Chemotherapy

• Oxaliplatin (Eloxatin) 85 mg/m² IV once on day 1

Targeted therapy

• Bevacizumab (Avastin) 10 mg/kg IV once on day 1

14-day cycle for a maximum of 14 cycles

References

1. 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 PubMed

Sunitinib monotherapy

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Regimen variant #1

Study	Evidence
Feldman et al. 2010	Phase II

Targeted therapy

• Sunitinib (Sutent) 37.5 mg PO once per day

42-day cycles

Regimen variant #2

Study	Years of enrollment	Evidence
Oechsle et al. 2011	2007-2010	Phase II

Targeted therapy

• Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28

42-day cycles

References

1. 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. link to original article contains verified protocol PubMed
2. 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. doi: 10.1200/JCO.2002.01.038. PMID: 12431967. link to original article PubMed

Patient information

• Testicular Cancer Resource Center - detailed website with information for patients and families about testicular cancer