Testicular Cancer Treatment Regimens

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Testicular Cancer Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are Category 2A unless otherwise indicated.

▶Primary Chemotherapy for Germ Cell Tumors1

REGIMEN

DOSING

Preferred Regimens

BEP (Bleomycin + Etoposide + Cisplatin)2,a,b

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes dailya

Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily

Days 1,8,15 OR Days 2,9,16: Bleomycin 30 units IV over 10 minutes daily.

Repeat cycle every 3 weeks for 3-4 cyclesb (seminoma) or 1, 3, or 4 cyclesb (nonseminoma).

EP (Cisplatin + Etoposide)3,a,c

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes dailya

Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4 cycles.c

Other Recommended Regimens

Carboplatin (for patients with stage IA, IB seminoma)4-6

Day 1: Carboplatin AUC 7 over 30 minutes.

Repeat cycle every 3 weeks for 1-2 cycles.

VIP (Etoposide + Ifosfamide + Mesna + Cisplatin; for intermediate risk patients with stage IIC, III seminoma or intermediate risk patients with stage IIIB nonseminoma or selected patients with poor-risk, stage IIIC nonseminoma)7,a,d-f

Days 1-5: Etoposide 75mg/m2 IV over 60 minutes daily

Days 1-5: Mesna 240mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from start of each Ifosfamide dosee

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes daily.a

Repeat cycle every 3 weeks for 4 cycles.

▶Adjuvant Chemotherapy Following Resection of Residual Germ Cell Tumors1,g,h

EP (Cisplatin + Etoposide)3,a,h

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes dailya

Days 1-5: Etoposide 100mg/m2 over 60 minutes.

Repeat every 3 weeks for 2 cycles.

TIP (Paclitaxel + Ifosfamide + Cisplatin)8,a,e,i

Day 1: Paclitaxel 250mg/m2 IV continuous infusion over 24 hours

Days 2-5: Mesna 300mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dosee

Days 2-5: Ifosfamide 1,500mg/m2 IV over 3 hours dailyd

Days 2-5: Cisplatin 25mg/m2 IV over 60 minutes daily.a

Repeat cycle every 3 weeks for 2 cycles.

VIP (Etoposide + Ifosfamide + Mesna + Cisplatin)7,a,d,e

Days 1-5: Etoposide 75mg/m2 IV over 60 minutes daily

Days 1-5: Mesna 240mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from start of each Ifosfamide dose daily

Days 1-5: Ifosfamide 1,200mg/m2 IV over 3 hours dailye

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes daily.a

Repeat cycle every 3 weeks for 2 cycles.

VeIP (Etoposide + Ifosfamide + Cisplatin)9,10,a,e,i

Days 1-2: Vinblastine 0.11mg/kg IV over 5-10 minutes daily

Dasy 1-5: Mesna 240mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose dailye

Days 1-5: Ifosfamide 1,200mg/m2 IV over 3 hours daily

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 2 cycles.

▶Post-Surgical Chemotherapy Following Retroperitoneal Lymph Node Dissection for Nonseminoma Tumors1

BEP (Bleomycin + Etoposide + Cisplatin)2,a,j

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes dailya

Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily

Days 1,8,15 OR Days 2,9,16: Bleomycin 30 units IV over 10 minutes daily.

Repeat cycle every 3 weeks for 2 or 3 cycles.j

EP (Cisplatin + Etoposide)3,a,g,j

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes dailya

Days 1-5: Etoposide 100mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 2 or 4 cycles.j

▶Second-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors1,k

Conventional-Dose Chemotherapy Regimens

Preferred Regimens

TIP (Paclitaxel + Ifosfamide + Cisplatin)8,e,i,k

Day 1: Paclitaxel 250mg/m2 IV continuous infusion over 24 hours

Days 2-5: Mesna 300mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose

Days 2-5: Ifosfamide 1,500mg/m2 IV over 3 hours dailye

Days 2-5: Cisplatin 25mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4 cycles.

VeIP (Etoposide + Ifosfamide + Cisplatin)9,10,a,e,i,k

Days 1-2: Vinblastine 0.11mg/kg IV over 5-10 minutes daily

Days 1-5: Mesna 240mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose dailye

Days 1-5: Ifosfamide 1,200mg/m2 IV over 3 hours daily

Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes daily.

Repeat cycle every 3 weeks for 4 cycles.

High-Dose Chemotherapy Regimens

Preferred Regimens

Carboplatin + Etoposide11

Carboplatin 700mg/m2 IV

Etoposide 750mg/m2 IV.

Administer 5, 4 and 3 days before peripheral blood stem cell infusion for 2 cycles.

Paclitaxel + Ifosfamide + Carboplatin + Etoposide12-14,e

Day 1: Paclitaxel 200mg/m2 IV over 24 hours

Days 2-4: Ifosfamide 2000mg/m2 IV over 4 hours with Mesna protection.e

Repeat every 2 weeks for 2 cycles, followed by:

Days 1-3: Carboplatin AUC 7-8 IV over 60 minutes

Days 1-3: Etoposide 400mg/m2 IV.

Administer with peripheral blood stem cell support at 14- to 21-day intervals for 3 cycles.

▶Third-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors: High-Dose Chemotherapy NOT Previously Received1,k

Preferred Regimens (High-Dose Chemotherapy)

Carboplatin + Etoposide11

Carboplatin 700mg/m2 IV

Etoposide 750mg/m2 IV.

Administer 5, 4 and 3 days before peripheral blood stem cell infusion for 2 cycles.

Paclitaxel + Ifosfamide + Carboplatin + Etoposide12-14,e

Day 1: Paclitaxel 200mg/m2 IV over 24 hours

Days 2-4: Ifosfamide 2000mg/m2 IV over 4 hours with Mesna protection.e

Repeat every 2 weeks for 2 cycles, followed by:

Days 1-3: Carboplatin AUC 7-8 IV over 60 minutes

Days 1-3: Etoposide 400mg/m2 IV.

Administer with peripheral blood stem cell support at 14- to 21-day intervals for 3 cycles.

Other Recommended Regimens

Gemcitabine + Paclitaxel + Oxaliplatin15

Days 1,8: Paclitaxel 80mg/m2 IV over 60 minutes

Days 1,8: Gemcitabine 800mg/m2 IV over 30 minutes

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + Oxaliplatin16-18

Days 1,8: Gemicitabine 1000-1.250mg/m2 IV over 30 minutes

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Gemcitabine + Paclitaxel19,20

Days 1,8,15: Paclitaxel 100mg/m2 IV over 60 minutes

Days 1,8,15: Gemicitabine 1,000mg/m2 IV over 30 minutes.

Repeat every 4 weeks for 6 cycles.

Etoposide (oral)21

Days 1-21: Etoposide 50-100 mg orally daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Pembrolizumab (for MSI-H/dMMR tumors)22-24

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

▶Third-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors: High-Dose Chemotherapy Previously Received1,k

Preferred Regimens

Gemcitabine + Paclitaxel + Oxaliplatin15

Days 1,8: Paclitaxel 80mg/m2 IV over 60 minutes

Days 1,8: Gemcitabine 800mg/m2 IV over 30 minutes

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 8 cycles.

Gemicitabine + Oxaliplatin16-18

Days 1,8: Gemicitabine 1000-1.250mg/m2 IV over 30 minutes

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Gemcitabine + Paclitaxel19,20

Days 1,8,15: Paclitaxel 100mg/m2 IV over 60 minutes

Days 1,8,15: Gemicitabine 1,000mg/m2 IV over 30 minutes.

Repeat every 4 weeks for 6 cycles.

Etoposide (oral)21

Days 1-21: Etoposide 50-100 mg orally daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Pembrolizumab (for MSI-H/dMMR tumors)22-24

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

a.  Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin.

b.  For stage IIA, IIB, IIC, or III (seminoma) with Category 1 designation for stage IIC, III good or intermediate risk disease; or stage I-IIIC (nonseminoma) with Category 1 designation for 1S, IIA (S1), IIB (S1), IIC, IIIA, IIIB, IIIC disease. Number of cycles dependent on stage of disease.

c.  For stage II-III (seminoma) with Category 1 designation for stage IIC, III good-risk disease; or stage IS, IIA (S1), IIB (S1), IIC, IIIA (nonseminoma) with Category 1 designation.

d.  VIP: This regimen is high risk for febrile neutropenia and granulocyte colony-stimulating factors (G-CSFs) should be used (See NCCN Guidelines for Hematopoietic Growth Factors).

e.  Hydration is required pre- and post-administration of Ifosfamide.

f.  Category 1 for intermediate-risk stage IIIB disease and poor-risk stage IIIC disease (nonseminoma).

g. In the case of seminoma, adjuvant chemotherapy should be considered following complete resection of all residual disease. If resection incomplete, full course of second-line chemotherapy is recommended. If a biopsy is performed and is positive, consider surgery if complete resection is possible, or full course of second-line chemotherapy.

h. Consider EP for low-volume, residual embryonal, yolk sac, choriocarcinoma, or seminoma element (nonseminoma).

i.  TIP, VeIP: These regimens are high risk for febrile neutropenia and G-CSFs should be used (See NCCN Guidelines for Hematopoietic Growth Factors).

j.  Number of cycles is dependent on nodal status.

k. If VeIP or TIP received as second-line therapy, high-dose chemotherapy is the preferred third-line option.

References

  1. Referenced with permission form the NCCN Clinical Practice Guidelines in Oncology™, Testicular Cancer, v1.2020. https://www.nccn.org/professionals/physician_gls/pdf/testicular.pdf. Accessed November 11, 2019.

  2. 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 Indian University experience. J Clin Oncol. 1998;16:702-706.

  3. Xiao H, Mazumdar M, Bajorin DF, et al. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997;15:2553-2558.

  4. Oliver RT, Mason MD, Mead GM, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005;366:293-300.

  5. Oliver RT, Mead GM, Rustin GJ, et al. 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;29:957-962.

  6. Aparicio J, Germà JR, García del Muro X, et al. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol. 2005;23:8717-8723.

  7. Nichols CR, Catalano PJ, Crawford ED, et al. 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;16:1287-1293.

  8. Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005;23:6549-6555.

  9. Loehrer PJ Sr, Gonin R, Nichols CR, et al. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998;16:2500-2504.

10. Loehrer PJ Sr, Lauer R, Roth BJ, et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med. 1988;109:540-546.

11. Einhorn LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007;357:340-348.

12. Feldman DR, Sheinfeld J, Bajorin DF, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010;28:1706-1713.

13. Moeung S, Chevreau C, Broutin S, et al. Therapeutic drug monitoring of carboplatin in high-dose protocol (TI-CE) for advanced germ cell tumors: Pharmacokinetic results of a phase II multicenter study. Clin Cancer Res. 2017;23:7171-7179.

14. Kondagunta GV, Bacik J, Sheinfeld J, et al. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007;25:85-90.

15. Bokemeyer C, Oechsle K, Honecker F, et al. 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;19:448-453.

16. Pectasides D, Pectasides M, Farmakis D, et al. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol. 2004;15:493-497.

17. Kollmannsberger C, Beyer J, Liersch R, et al. 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;22:108-114.

18. De Giorgi U, Rosti G, Aieta M, et al. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol. 2006;50:1032-1038.

19. 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;25:513-516.

20. Mulherin BP, Brames MJ, Einhorn LH. Long-term survival with paclitaxel and gemcitabine for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. Am J Clin Oncol. 2015;38:373-376.

21. Miller JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990;17(1 Suppl 2):36-9.

22. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2019.

23. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409-413.

24. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509-2520.

(Revised 11/2019) © 2019 by Haymarket Media, Inc.

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AFINITOR AVASTIN CABOMETYX
Cisplatin COSMEGEN DEPO-PROVERA
Doxorubicin HCl Doxorubicin HCl Solution INLYTA
LENVIMA NEXAVAR OPDIVO
PROLEUKIN SUTENT TECENTRIQ
Thiotepa TICE BCG TORISEL
VALSTAR VINCASAR PFS VOTRIENT


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Bleomycin CASODEX Cisplatin
COSMEGEN DELESTROGEN ELIGARD
EMCYT ESTRACE ETOPOPHOS
FIRMAGON Flutamide IFEX
JEVTANA Leuprolide acetate LUPRON DEPOT 7.5mg
LUPRON DEPOT-3 MONTH 22.5mg LUPRON DEPOT-4 MONTH 30mg LUPRON DEPOT-6 MONTH 45mg
MENEST Mitoxantrone HCl NILANDRON
PREMARIN PROVENGE TAXOTERE
TOPOSAR TRELSTAR VANTAS
Vinblastine for injection Vinblastine injection XOFIGO
XTANDI ZOLADEX ZOLADEX 3-MONTH 10.8mg
ZYTIGA
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