Difference between revisions of "Testicular cancer"

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<!-- # '''Abstract:''' A. Jain, M. J. Brames, D. J. Vaughn, L. H. Einhorn. Phase II clinical trial of oxaliplatin and bevacizumab in refractory metastatic germ cell tumors (GCT). J Clin Oncol 29: 2011 (suppl; abstr 4579). [http://meetinglibrary.asco.org/content/75952-102 link to abstract] '''contains verified protocol''' -->
 
<!-- # '''Abstract:''' A. Jain, M. J. Brames, D. J. Vaughn, L. H. Einhorn. Phase II clinical trial of oxaliplatin and bevacizumab in refractory metastatic germ cell tumors (GCT). J Clin Oncol 29: 2011 (suppl; abstr 4579). [http://meetinglibrary.asco.org/content/75952-102 link to abstract] '''contains verified protocol''' -->
 
# 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. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2014&issue=10000&article=00006&type=abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23388561 PubMed]
 
# 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. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2014&issue=10000&article=00006&type=abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23388561 PubMed]
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==Plicamycin monotherapy {{#subobject:7680fd|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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===Regimen {{#subobject:1df196|Variant=1}}===
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{| class="wikitable" style="width: 100%; text-align:center;"
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!style="width: 50%"|Study
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!style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]]
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|[https://www.nejm.org/doi/full/10.1056/NEJM196501212720301 Brown & Kennedy 1965]
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| style="background-color:#ffffbe" |Non-randomized, <20 pts
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''Of historic interest.''
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====Chemotherapy====
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*[[Plicamycin (Mithracin)]]
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===References===
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# Brown JH, Kennedy BJ. Mithramycin in the treatment of disseminated testicular neoplasms. N Engl J Med. 1965 Jan 21;272:111-8. [https://www.nejm.org/doi/full/10.1056/NEJM196501212720301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14224214 PubMed]
  
 
==Sunitinib monotherapy {{#subobject:a97a47|Regimen=1}}==
 
==Sunitinib monotherapy {{#subobject:a97a47|Regimen=1}}==

Revision as of 02:50, 2 December 2018

Section editor
ChenEddy Sept2016.jpg
 Eddy J. Chen, MD
Boston, MA

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

Older

NCCN

Adjuvant therapy for resectable disease

BEP

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BEP: Bleomycin, Etoposide, Platinol (Cisplatin)

Regimen

Study Evidence Comparator 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

BVP

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BVP: Bleomycin, Vinblastine, Platinol (Cisplatin)
PVB: Platinol (Cisplatin), Vinblastine, Bleomycin

Regimen

Study Evidence Comparator Efficacy
Williams et al. 1987 Phase III (E) Observation Superior RFS

Included for historical purposes, only.

Preceding treatment

Chemotherapy

28-day cycle for 2 cycles

References

  1. Williams SD, Stablein DM, Einhorn LH, Muggia FM, Weiss RB, Donohue JP, Paulson DF, Brunner KW, Jacobs EM, Spaulding JT, DeWys WD, Crawford ED. Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med. 1987 Dec 3;317(23):1433-8. link to original article PubMed

Carboplatin monotherapy

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Variant #1

Study Evidence Comparator 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 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, "standard" BEP x 3

Study Evidence Comparator 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 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

Chemotherapy

21-day cycle for 3 cycles

Variant #2, "standard" BEP x 4

Study Evidence Comparator Efficacy
Williams et al. 1987 Phase III (E) BVP Seems to have superior OS
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. 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 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, 3-day etoposide x 3

Study Evidence Comparator 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, 3-day etoposide x 4

Study Evidence Comparator 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, 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
  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

Bleomycin & Vinblastine

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Regimen

Study Evidence
Peckham et al. 1979 Non-randomized

Here for historic purposes.

Chemotherapy

References

  1. Peckham MJ, McElwain TJ, Barrett A, Hendry WF. Combined management of malignant teratoma of the testis. Lancet. 1979 Aug 11;2(8137):267-70. lnk to original article 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

BVP

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BVP: Bleomycin, Vinblastine, Platinol (Cisplatin)
PVB: Platinol (Cisplatin), Vinblastine, Bleomycin

Regimen

Study Evidence Comparator Efficacy
Einhorn & Donohue 1977 Non-randomized
Einhorn et al. 1981 Phase III (C) ABVP Seems not superior
Stoter et al. 1986 Phase III (C) Dose de-escalated PVB Seems not superior
Williams et al. 1987 Phase III (C) BEP Seems to have inferior OS

Included for historical purposes, only.

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • Einhorn et al. 1981: Vinblastine maintenance versus no further treatment

References

  1. Einhorn LH, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977 Sep;87(3):293-8. link to original article PubMed
  2. Einhorn LH, Williams SD, Troner M, Birch R, Greco FA. The role of maintenance therapy in disseminated testicular cancer. N Engl J Med. 1981 Sep 24;305(13):727-31. link to original article PubMed
  3. Stoter G, Sleyfer DT, ten Bokkel Huinink WW, Kaye SB, Jones WG, van Oosterom AT, Vendrik CP, Spaander P, de Pauw M, Sylvester R. High-dose versus low-dose vinblastine in cisplatin-vinblastine-bleomycin combination chemotherapy of non-seminomatous testicular cancer: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group. J Clin Oncol. 1986 Aug;4(8):1199-206. link to original article PubMed
  4. 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

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

Regimen

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

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

Cisplatin & Etoposide

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EP: Etoposide, Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Bosl et al. 1988 Phase III (C) 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

VIP

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

Regimen

Study Evidence Comparator 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. 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"

Subsequent treatment

Maintenance therapy

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

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

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

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

TIP

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

Regimen

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

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
  • 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

VIP

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

Regimen

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

Chemotherapy

1 cycle

Subsequent treatment

References

  1. 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. 2007 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

GemOx

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GEMOX: GEMcitabine, OXaliplatin

Regimen

Study Evidence
Pectasides et al. 2004 Phase II

Chemotherapy

Supportive medications

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

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. 2007 Phase II

Chemotherapy

Supportive medications

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

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

Plicamycin monotherapy

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Regimen

Study Evidence
Brown & Kennedy 1965 Non-randomized, <20 pts

Of historic interest.

Chemotherapy

References

  1. Brown JH, Kennedy BJ. Mithramycin in the treatment of disseminated testicular neoplasms. N Engl J Med. 1965 Jan 21;272:111-8. 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

Patient information

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