Recurrent Testicular Cancer
Current Clinical Trials
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Deciding on further treatment depends on many factors, including the specific
cancer, prior treatment, site of recurrence, and individual patient
considerations. Salvage regimens consisting of ifosfamide, cisplatin, and
either etoposide or vinblastine can induce long-term complete responses in
about 25% of patients with disease that has persisted or recurred
following other cisplatin-based regimens. Patients who have had an initial
complete response to first-line chemotherapy and those without extensive
disease have the most favorable outcomes.[1,2] This regimen is now the standard
initial salvage regimen.[2,3] Few, if any, patients with recurrent
nonseminomatous germ cell tumors of extragonadal origin, however, achieve long-term
disease-free survival (DFS) using vinblastine, ifosfamide, and cisplatin if their
disease recurred after they received an initial regimen containing etoposide
and cisplatin.[2][Level of evidence: 3iiDii] High-dose chemotherapy with
autologous marrow transplantation has also been used in uncontrolled case series in the
setting of recurrent disease.[4-11] However, a randomized controlled trial comparing conventional doses of salvage chemotherapy with high-dose chemotherapy with autologous marrow rescue showed more toxic effects and treatment-related deaths in the high-dose arm without any improvement in response rate or overall survival.[12][Level of evidence: 1iiA] In some highly selected patients with chemorefractory
disease confined to a single site, surgical resection may yield long-term
DFS.[13,14] One case series suggests that a maintenance regimen of daily oral
etoposide (taken 21 days out of 28 days) may benefit patients who achieve a complete
remission after salvage therapy.[15]
A special case of late relapse may include patients who relapse more than 2 years
after achieving complete remission; this population represents less than 5% of
patients who are in complete remission after 2 years. Results with
chemotherapy are poor in this patient subset, and surgical treatment appears to
be superior, if technically feasible.[16] Teratoma may be
amenable to surgery at relapse, and teratoma also has a better prognosis than carcinoma after late
relapse. Teratoma is a relatively resistant histologic subtype,
so chemotherapy may not be appropriate.
Clinical trials are appropriate and should be considered whenever possible,
including phase I and phase II studies for those patients who do not achieve a complete
remission with induction therapy, or who do not achieve a complete remission
following etoposide and cisplatin for their initial relapse, or for patients who
have a second relapse.[17]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
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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 109 (7): 540-6, 1988.
[PUBMED Abstract]
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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 16 (7): 2500-4, 1998.
[PUBMED Abstract]
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Motzer RJ, Cooper K, Geller NL, et al.: The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. Cancer 66 (12): 2476-81, 1990.
[PUBMED Abstract]
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Broun ER, Nichols CR, Kneebone P, et al.: Long-term outcome of patients with relapsed and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue. Ann Intern Med 117 (2): 124-8, 1992.
[PUBMED Abstract]
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Droz JP, Pico JL, Ghosn M, et al.: Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer. Eur J Cancer 27 (7): 831-5, 1991.
[PUBMED Abstract]
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Cullen MH: Dose-response relationships in testicular cancer. Eur J Cancer 27 (7): 817-8, 1991.
[PUBMED Abstract]
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Motzer RJ, Mazumdar M, Bosl GJ, et al.: High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity. J Clin Oncol 14 (4): 1098-105, 1996.
[PUBMED Abstract]
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Motzer RJ, Bosl GJ: High-dose chemotherapy for resistant germ cell tumors: recent advances and future directions. J Natl Cancer Inst 84 (22): 1703-9, 1992.
[PUBMED Abstract]
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Bhatia S, Abonour R, Porcu P, et al.: High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer. J Clin Oncol 18 (19): 3346-51, 2000.
[PUBMED Abstract]
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Beyer J, Kramar A, Mandanas R, et al.: High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables. J Clin Oncol 14 (10): 2638-45, 1996.
[PUBMED Abstract]
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Einhorn LH, Williams SD, Chamness A, et al.: High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 357 (4): 340-8, 2007.
[PUBMED Abstract]
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Pico JL, Rosti G, Kramar A, et al.: 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 16 (7): 1152-9, 2005.
[PUBMED Abstract]
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Murphy BR, Breeden ES, Donohue JP, et al.: Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol 11 (2): 324-9, 1993.
[PUBMED Abstract]
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Fox EP, Weathers TD, Williams SD, et al.: Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections. J Clin Oncol 11 (7): 1294-9, 1993.
[PUBMED Abstract]
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Cooper MA, Einhorn LH: Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors. J Clin Oncol 13 (5): 1167-9, 1995.
[PUBMED Abstract]
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Baniel J, Foster RS, Gonin R, et al.: Late relapse of testicular cancer. J Clin Oncol 13 (5): 1170-6, 1995.
[PUBMED Abstract]
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Motzer RJ, Geller NL, Tan CC, et al.: Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989). Cancer 67 (5): 1305-10, 1991.
[PUBMED Abstract]
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