Testicular cancer

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Eddy J. Chen, MD
Massachusetts General Hospital
Boston, MA

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

Contents


Guidelines

ESMO

Older

NCCN

Adjuvant therapy for resectable disease

BEP

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BEP: Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study Evidence Comparator Comparative Efficacy
Albers et al. 2008 (AUO AH 01/94) Phase III (E) RPLND Superior RFS

Preceding treatment

Chemotherapy

1 cycle

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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Variant #1

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

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-time dose

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

Chemotherapy

Supportive medications

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 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
  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; 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
  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. 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 Comparative Efficacy
Jones et al. 2005 (MRC TE18/EORTC 30942) Phase III (C) Lower-dose RT Seems not superior
Oliver et al. 2005 (MRC TE19/EORTC 30982) Phase III (C) Carboplatin Seems to have non-inferior RFS

Note: radiation details are available in the references.

Preceding treatment

Radiotherapy

References

  1. MRC TE18/EORTC 30942: Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, Stenning SP. 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 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

Upfront therapy for disseminated disease

BEP

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

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

Study Evidence Comparator Comparative Efficacy
Einhorn et al. 1989 Phase III (E) BEP x 4 Seems to have equivalent DFS
Toner et al. 2001 Phase III (C) Modified BEP 30/360/100 Seems to have superior OS (*)
de Wit et al. 2001 Phase III (E) 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

21-day cycle for 3 cycles

Variant #2, 90/500/100 x 4 ("standard" BEP)

Study Evidence Comparator Comparative Efficacy
Williams et al. 1987a Phase III (E) BVP Seems not superior (*)
Einhorn et al. 1989 Phase III (C) BEP x 3 Seems to have equivalent DFS
Nichols et al. 1998 (ECOG E3887) Phase III (C) VIP Seems not superior
de Wit et al. 2001 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
Motzer et al. 2007 Phase III (C) BEP x 2, then HDCT x 2 Seems not superior
Culine et al. 2008 (T93MP) Phase III (C) CISCA/VB Seems not superior
Daugaard et al. 2010 (EORTC 30974) Phase III (C) BEP x 1, then HDCT x 3 Seems not superior
de Wit et al. 2012 (EORTC 30983) Phase III (C) T-BEP Seems not superior
Fizazi et al. 2014 (GETUG 13) 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 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

Variant #3, 90/495/100 x 3 (3-day etoposide)

Study Evidence Comparator Comparative Efficacy
de Wit et al. 2001 Phase III (E) 1. BEP x 3
2. BEP x 4
Equivalent PFS
3. BEP, 3-day etoposide x 4 Equivalent PFS

Chemotherapy

21-day cycle for 3 cycles

Variant #4, 90/495/100 x 4 (3-day etoposide)

Study Evidence Comparator Comparative Efficacy
de Wit et al. 2001 Phase III (E) 1. BEP x 3
2. BEP x 4
Equivalent PFS
3. BEP, 3-day etoposide x 3 Equivalent PFS

Chemotherapy

21-day cycle for 4 cycles

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

Part 3: Modified BEP

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. 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. 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
  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 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
  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
  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

Accelerated BEP

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

Regimen

Study Evidence
Grimison et al. 2014 Phase II

Chemotherapy

Supportive medications

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

BO

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BO: Bleomycin & Oncovin (Vincristine)

Regimen

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

Preceding treatment

Chemotherapy

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 Evidence
Fosså et al. 2005 (EORTC 30948) Phase II
Huddart et al. 2014 (MRC TE23) Randomized Phase II (E)

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

14-day cycle for 2 cycles

Subsequent treatment

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

Cisplatin & Etoposide

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EP: Etoposide, Platinol (Cisplatin)

Regimen

Study Evidence Comparator Comparative Efficacy
Bosl et al. 1988 Phase III (E) VAB-6 Seems not superior
Bajorin et al. 1993 Phase III (C) EC Seems to have superior EFS

Chemotherapy

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

Supportive medications

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 SD article PubMed

PVeBV

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

Regimen

Study Evidence Comparator Comparative Efficacy
Chevreau et al. 1993 Phase III (C) PVeBV, then PEC with auto HSCT Seems not superior

Chemotherapy

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 (GETUG). 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 Evidence Comparator Comparative Efficacy
Nichols et al. 1998 (ECOG E3887) Phase III (E) BEP Seems not superior

Chemotherapy

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 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. 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

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

Supportive medications

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 Evidence
Fizazi et al. 2014 (GIP-TG) Phase II

Chemotherapy

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

Ifosfamide & Paclitaxel

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TI: Taxol (Paclitaxel) & Ifosfamide

Regimen

Study Evidence
Kondagunta et al. 2007 Phase II

Chemotherapy, TI portion

Supportive medications

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

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)

Variant #1, 175/6000/100

Study Evidence
Kurobe et al. 2014 Phase II

Chemotherapy

Supportive medications

21-day cycle for 4 cycles

Variant #2, 250/6000/100

Study Evidence
Kondagunta et al. 2005 Phase II

Chemotherapy

Supportive medications

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 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

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

Variant #1, 1 cycle

Study Evidence Comparator Comparative Efficacy
Lorch et al. 2007 Phase III (C) VIP x 3, then CEC with auto HSCT Seems not superior

Chemotherapy

1 cycle

Subsequent treatment

Variant #2, 4 cycles

Study Evidence Comparator Comparative Efficacy
Pico et al. 2005 (IT 94) Phase III (C) VIP x 3, then CarboPEC with auto HSCT Seems not superior

Chemotherapy

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 (GETUG-FNCLCC), France; European Group for Blood and Marrow Transplantation (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

Chemotherapy

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

Chemotherapy

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

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

Variant #1, 2000/130

Study Evidence
Kollmannsberger et al. 2004 Phase II
Pectasides et al. 2004 Phase II

Chemotherapy

Supportive medications

21-day cycle for up to 6 cycles

Variant #2, 2500/130

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

Chemotherapy

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. 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 Evidence
Bokemeyer et al. 2007 Phase II

Chemotherapy

Supportive medications

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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Variant #1

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

Chemotherapy

Supportive medications

28-day cycle for up to 6 cycles

Variant #2

Study Evidence
Einhorn et al. 2007b Phase II

Chemotherapy

Supportive medications

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

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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Variant #1

Study Evidence
Feldman et al. 2010 Phase II

Chemotherapy

Continued indefinitely

Variant #2

Study Evidence
Oechsle et al. 2011 Phase II

Chemotherapy

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

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