Testicular cancer - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main testicular cancer page for current regimens.

7 regimens on this page 7 variants on this page

Adjuvant therapy for resectable disease

BVP

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Williams et al. 1987	1979-1984	Phase 3 (E-esc)	Observation	Superior RFS

Preceding treatment

• Orchiectomy & RPLND

Chemotherapy

• Bleomycin (Blenoxane) 30 units (route not specified) once per day on days 1, 8, 15, 22
• Vinblastine (Velban) 0.15 mg/kg IV bolus once per day on days 1 & 2
• Cisplatin (Platinol) 20 mg/m² IV over 15 to 30 minutes once per day on days 1 to 5

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 contains dosing details in manuscript PubMed

VAB-6

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Williams et al. 1987	1979-1984	Phase 3 (E-esc)	Observation	Superior RFS

Preceding treatment

• Orchiectomy & RPLND

Chemotherapy

• Bleomycin (Blenoxane) 30 units IV bolus once on day 1, then 15 units/m²/day IV continuous infusion over 144 hours (total dose per cycle: 120 units)
• Cisplatin (Platinol) 120 mg/m² IV over 60 minutes once on day 7
• Cyclophosphamide (Cytoxan) 600 mg/m² IV bolus once on day 1
• Dactinomycin (Cosmegen) 1 mg/m² IV bolus once on day 1
• Vinblastine (Velban) 4 mg/m² IV bolus once on day 1

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 contains dosing details in manuscript PubMed

Upfront therapy for disseminated disease

Bleomycin & Vinblastine

Regimen

Study	Evidence
Peckham et al. 1979	Non-randomized

Chemotherapy

• Bleomycin (Blenoxane) 30 mg/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 150 mg)
• Vinblastine (Velban) 15 mg/m² IV once per day on days 1 & 2

28- to 35-day cycle for 6 cycles

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 contains dosing details in manuscript PubMed

BVP

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Einhorn & Donohue 1977	1974-NR	Non-randomized
Stoter et al. 1979	1976-NR	Non-randomized
Einhorn et al. 1981	1978-1980	Phase 3 (C)	ABVP	Did not meet efficacy endpoints
Garnick et al. 1983	NR	Non-randomized
Samson et al. 1984 (SWOG S7817)	1978-07 to 1981-04	Phase 3 (E-esc)	BVP; dose de-escalated	Superior OS
Stoter et al. 1986	1979-1983	Phase 3 (C)	BVP; dose de-escalated	Did not meet efficacy endpoints
Williams et al. 1987a	1982-1984	Phase 3 (C)	BEP	Did not meet primary endpoint of OS1
Wozniak et al. 1991	1982-1986	Phase 3 (C)	VPV	Did not meet co-primary endpoints of CR rate/OS

¹In Williams et al. 1987a, there seemed to be a survival disadvantage in the high tumor volume subgroup, but no difference was seen in the overall group.

Chemotherapy

• Bleomycin (Blenoxane) 15 units/m² IM or IV once per day on days 1, 4, 8, 11, 15, 18 (twice per week)
• Vinblastine (Velban) 12 mg/m² IV once on day 1
• Cisplatin (Platinol) 120 mg/m² IV once on day 3

21-day cycle for 4 cycles

Subsequent treatment

• Einhorn et al. 1981: Vinblastine maintenance versus no further treatment
• Garnick et al. 1983: Tumor-reductive surgery, then adjuvant AC

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. Stoter G, Sleijfer DT, Vendrik CP, Schraffordt Koops H, Struyvenberg A, Van Oosterom AT, Brouwers TM, Pinedo HM. Combination chemotherapy with cis-diammine-dichloro-platinum, vinblastine, and bleomycin in advanced testicular non-seminoma. Lancet. 1979 May 5;1(8123):941-5. link to original article PubMed
3. 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
4. Garnick MB, Canellos GP, Richie JP. Treatment and surgical staging of testicular and primary extragonadal germ cell cancer. JAMA. 1983 Oct 7;250(13):1733-41. link to original article PubMed
5. SWOG S7817: Samson MK, Rivkin SE, Jones SE, Costanzi JJ, LoBuglio AF, Stephens RL, Gehan EA, Cummings GD. Dose-response and dose-survival advantage for high versus low-dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer: A Southwest Oncology Group study. Cancer. 1984 Mar 1;53(5):1029-35. link to original article contains dosing details in manuscript PubMed
6. Stoter G, Sleyfer DT, ten Bokkel Huinink WW, Kaye SB, Jones WG, van Oosterom AT, Vendrik CP, Spaander P, de Pauw M, Sylvester R; EORTC Genitourinary Tract Cancer Cooperative Group. 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
7. 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 dosing details in manuscript PubMed
8. Wozniak AJ, Samson MK, Shah NT, Crawford ED, Ford CD, Altman SJ, Stephens RL, Natale RB, Bouroncle BA, Blumenstein BA, Cummings GD; Southwest Oncology Group. A randomized trial of cisplatin, vinblastine, and bleomycin versus vinblastine, cisplatin, and etoposide in the treatment of advanced germ cell tumors of the testis: a Southwest Oncology Group study. J Clin Oncol. 1991 Jan;9(1):70-6. link to original article contains dosing details in manuscript PubMed

Chlorambucil, Dactinomycin, Methotrexate

Regimen

Study	Dates of enrollment	Evidence
Li et al. 1960	1958-1959	Non-randomized

Note: this is likely the first trial of combination chemotherapy in solid tumors.

Chemotherapy

• Chlorambucil (Leukeran) 10 mg PO once per day on days 1 to 25
• Dactinomycin (Cosmegen) 0.5 mg IV once per day on days 3 to 7, 12 to 16, 21 to 25
• Methotrexate (MTX) 5 mg PO once per day on days 1 to 25

25-day course

References

1. Li MC, Whitmore WF Jr, Golbey R, Grabstald H. Effects of combined drug therapy on metastatic cancer of the testis. JAMA. 1960 Nov 5;174:1291-9. link to original article contains dosing details in manuscript PubMed

CISCA/VB

CISCA/VB: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin) alternating with Vinblastine & Bleomycin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fizazi et al. 2002	1987-1993	Phase 3 (C)	CISCA/VB; dose de-escalated	Did not meet primary endpoint of CR rate at 18 mo
Culine et al. 2008 (T93MP)	1994-2000	Phase 3 (E-esc)	BEP	Did not meet primary endpoint of FRR

Chemotherapy, CISCA portion (cycles 1 & 3)

• Cisplatin (Platinol) 120 mg/m² IV once on day 3
• Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 2
• Doxorubicin (Adriamycin) 45 mg/m² IV once per day on days 1 & 2

Chemotherapy, VB portion (cycles 2 & 4)

• Vinblastine (Velban) 3 mg/m² IV once per day on days 1 to 5
• Bleomycin (Blenoxane) 30 units IV once per day on days 1 to 5

21-day cycle for at least 4 cycles

References

1. Fizazi K, Do KA, Wang X, Finn L, Logothetis CJ, Amato RJ. A 20% dose reduction of the original CISCA/VB regimen allows better tolerance and similar survival rate in disseminated testicular non-seminomatous germ-cell tumors: final results of a phase III randomized trial. Ann Oncol. 2002 Jan;13(1):125-34. link to original article contains dosing details in manuscript PubMed
2. T93MP: Culine S, Kramar A, Théodore C, Geoffrois L, Chevreau C, Biron P, Nguyen BB, Héron JF, Kerbrat P, Caty A, Delva R, Fargeot P, Fizazi K, Bouzy J, Droz JP; Genito-Urinary Group of the French Federation of Cancer Centers. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol. 2008 Jan 20;26(3):421-7. link to original article contains dosing details in manuscript PubMed

VAB-6

Regimen

Study	Dates of enrollment	Evidence
Vugrin et al. 1981	1978-1979	Non-randomized (RT)
Bosl et al. 1986	1979-1982	Non-randomized (RT)

Chemotherapy

• Bleomycin (Blenoxane) as follows:
  • Cycles 1 & 2: 30 units IV push once on day 1, then 20 units/m²/day IV continuous infusion over 72 hours (total dose per cycle: 90 units)
• Cisplatin (Platinol) 120 mg/m² IV once on day 4
• Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1
• Dactinomycin (Cosmegen) 1 mg/m² IV once on day 1
• Vinblastine (Velban) 4 mg/m² IV once on day 1

28-day cycle for 3 cycles

References

1. Vugrin D, Herr HW, Whitmore WF Jr, Sogani PC, Golbey RB. VAB-6 combination chemotherapy in disseminated cancer of the testis. Ann Intern Med. 1981 Jul;95(1):59-61. link to original article contains dosing details in manuscript PubMed
2. Bosl GJ, Gluckman R, Geller NL, Golbey RB, Whitmore WF Jr, Herr H, Sogani P, Morse M, Martini N, Bains M, McCormack P. VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors. J Clin Oncol. 1986 Oct;4(10):1493-9. link to original article PubMed

Subsequent lines of therapy

Plicamycin monotherapy

Regimen

Study	Evidence
Brown & Kennedy 1965	Non-randomized, fewer than 20 pts
Ream et al. 1968	Non-randomized

Chemotherapy

• Plicamycin (Mithracin) 50 mcg/kg IV once per day on days 1 to 5

1-month cycles

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 contains dosing details in manuscript PubMed
2. Ream NW, Perlia CP, Wolter J, Taylor SG 3rd. Mithramycin therapy in disseminated germinal testicular cancer. JAMA. 1968 Jun 17;204(12):1030-6. link to original article PubMed