Testicular cancer

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Except for primary treatment for stage I disease, these regimens are generally applicable to seminoma and non-seminoma histologies.

24 regimens on this page 34 variants on this page

Guidelines

ESMO

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

NCCN

• NCCN Guidelines - Testicular Cancer

Primary treatment for stage I seminoma

Carboplatin monotherapy

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Regimen #1

Study	Evidence	Comparator	Efficacy
Oliver et al. 2005 (MRC TE19/EORTC 30982)	Phase III	Radiation therapy	Seems to have noninferior RFS

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-time dose

Regimen #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.

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. Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989 Nov;7(11):1748-56. link to original article contains verified formula PubMed
2. 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 TE19 collaborators and the EORTC 30982 collaborators. 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
   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
3. 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; Second 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
4. 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. 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	Evidence	Comparator	Efficacy
Oliver et al. 2005 (MRC TE19/EORTC 30982)	Phase III	Carboplatin	Seems to have noninferior RFS

Details are available in the reference.

References

1. 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 TE19 collaborators and the EORTC 30982 collaborators. 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
   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

Primary treatment

BEP

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BEP: Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen #1, "standard" BEP x 3

Study	Evidence	Comparator	Efficacy
Einhorn et al. 1989	Phase III	BEP x 4	Seems to have equivalent DFS
de Wit et al. 2001	Phase III	BEP x 4	Equivalent PFS
		BEP, 3-day etoposide x 3 BEP, 3-day etoposide x 4	Equivalent PFS

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 #2, "standard" BEP x 4

Study	Evidence	Comparator	Efficacy
Einhorn et al. 1989	Phase III	BEP x 3	Seems to have equivalent DFS
Nichols et al. 1998	Phase III	VIP	Seems not superior
de Wit et al. 2001	Phase III	BEP x 3	Equivalent PFS
		BEP, 3-day etoposide x 3 BEP, 3-day etoposide x 4	Equivalent PFS
Culine et al. 2008 (T93MP)	Phase III	CISCA/VB	Seems not superior

Chemotherapy

• Bleomycin (Blenoxane) 30 units IV bolus once per day on days 1, 8, 15
  • 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 30 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 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 5 mcg/kg SC once per day on days 7, 9 to 14, 16, 17

21-day cycle for 4 cycles

Regimen #3

Study	Evidence	Comparator	Efficacy
Williams et al. 1987	Phase III	BVP	Seems to have superior OS

Patients in Williams et al. 1987 had "advanced germ-cell tumors considered to be unsuitable for local therapy were eligible and included those with either testicular or extragonadal primary tumors. Patients with seminoma were eligible only if radiation therapy was considered to be inappropriate in their cases.

Chemotherapy

• Bleomycin (Blenoxane) 30 units IV bolus once per day on days 2, 9, 16
• Etoposide (Vepesid) 100 mg/m² IV over 30 minutes once per day on days 1 to 5
• Cisplatin (Platinol) 20 mg/m² IV over 15 to 30 minutes once per day on days 1 to 5

Supportive medications

• Normal saline 100 mL/hour IV on days of Cisplatin (Platinol)

21-day cycle for 4 cycles

Regimen #4, 3-day etoposide x 3

Study	Evidence	Comparator	Efficacy
de Wit et al. 2001	Phase III	BEP x 3 BEP x 4	Equivalent PFS
		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 #5, 3-day etoposide x 4

Study	Evidence	Comparator	Efficacy
de Wit et al. 2001	Phase III	BEP x 3 BEP x 4	Equivalent PFS
		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

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. 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. 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
4. de Wit R, Roberts JT, Wilkinson PM, de Mulder PH, Mead GM, Fosså SD, Cook P, de Prijck L, Stenning S, Collette L. 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 Organization 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
5. 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 Trial T93MP. 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

BVP

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BVP: Bleomycin, Vinblastine, Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Williams et al. 1987	Phase III	BEP	Seems to have inferior OS

Included for historical purposes, only.

Chemotherapy

• Bleomycin (Blenoxane) 30 units IV bolus once per day on days days 2, 9, 16
• Vinblastine (Velban)
• Cisplatin (Platinol) 20 mg/m² IV over 15 to 30 minutes once per day on days 1 to 5

Supportive medications

• Normal saline 100 mL/hour IV on days of Cisplatin (Platinol)

21-day cycle for 4 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

C-BOP/BEP

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

Regimen

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

Part 1: C-BOP

• Cisplatin (Platinol) 50 mg/m² IV once per day on days 1 & 2
• Cisplatin (Platinol) 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
• Bleomycin (Blenoxane) 15 mg continuous infusion on days 8 to 12
• Carboplatin (Paraplatin) AUC 3 IV once on day 8

14-day cycle for 2 cycles, followed by:

Part 2: BO

• Vincristine (Oncovin) 2 mg IV once per day on days 1 & 8
• Bleomycin (Blenoxane) 15 mg IV once per day on days 1 & 8

14-day cycle for 1 cycle, followed by:

Part 3: Modified BEP

• 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
• Bleomycin (Blenoxane) 15 mg IV on days 1, 8, and 15

21-day cycle for 3 cycles

References

1. 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

Cisplatin & Etoposide

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EP: Etoposide, Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Bosl et al. 1988	Phase III	VAB-6	Seems not superior
Bajorin et al. 1993	Phase III	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

VIP

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

Regimen

Study	Evidence	Comparator	Efficacy
Nichols et al. 1998	Phase III	BEP	Seems not superior

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 1 hour once per day on days 1 to 5

Supportive medications

• Mesna (Mesnex) 120 mg/m² IV slow push on day 1 before Ifosfamide (Ifex), then 1200 mg/m²/day IV continuous infusion on days 1 to 5 (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 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 5 mcg/kg SC once per day on days 7 to 16

21-day cycle for 4 cycles

References

1. 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

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. 2007	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.

High-dose 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"

"Most patients" who had complete or partial remission after two cycles of therapy received etoposide consolidation.

Maintenance therapy

• 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

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

Ifosfamide & Paclitaxel

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

Regimen

Study	Evidence
Kondagunta et al. 2007	Phase II

Chemotherapy, TI portion

• Paclitaxel (Taxol) 200 mg/m² IV over 24 hours once 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

Treatement followed by 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

TIP

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

Regimen

Study	Evidence
Kondagunta et al. 2005	Phase II

Chemotherapy

• Paclitaxel (Taxol) 250 mg/m² IV over 24 hours once 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) 500 mg/m² IV three times per day on days 2 to 5; prior to each dose of Ifosfamide (Ifex), 4 hours after each dose of Ifosfamide (Ifex), and 8 hours after each dose of Ifosfamide (Ifex)
• Dexamethasone (Decadron) 20 mg PO given twice on day 1, 14 and 7 hours prior to Paclitaxel (Taxol)
• Diphenhydramine (Benadryl) 50 mg IV once on day 1, 1 hour prior to Paclitaxel (Taxol)
• Cimetidine (Tagamet) 300 mg IV once on day 1, 1 hour 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

VeIP

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

Regimen

Study	Evidence
Loehrer et al. 1988	Phase II
Loehrer et al. 1998	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 1 hour 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 on days 1 to 5
• Normal saline 100 mL/hour IV continuous infusion on days 1 to 5

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

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. 2007	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

GemOx

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GEMOX: GEMcitabine, OXaliplatin

Regimen

Study	Evidence
Pectasides et al. 2004	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 before Gemcitabine (Gemzar), 12 hours after Gemcitabine (Gemzar), and 24 hours after Gemcitabine (Gemzar)

21-day cycle for up to 6 cycles

References

1. 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

Gemcitabine, Oxaliplatin, Paclitaxel

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GOP: Gemcitabine, Oxaliplatin, Paclitaxel

Regimen

Study	Evidence
Bokemeyer et al. 2007	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 1 hour 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 #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 1 hour once per day on days 1, 8, 15, given first

Supportive medications

• Dexamethasone (Decadron) 20 mg PO/IV 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)
• H2-blockade with ONE of the following, 60 minutes prior to each dose of Paclitaxel (Taxol):
  • Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15
  • Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15

28-day cycle for up to 6 cycles

Regimen #2

Study	Evidence
Einhorn et al. 2007	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 1 hour once per day on days 1, 8, 15, given first

Supportive medications

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

28-day cycle for up to 6 cycles

References

1. 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
• 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 #1

Study	Evidence
Feldman et al. 2010	Phase II

Chemotherapy

• Sunitinib (Sutent) 37.5 mg PO once per day for 6 weeks

Regimen #2

Study	Evidence
Oechsle et al. 2011	Phase II

Chemotherapy

• 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. 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

Patient information

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