Standard Treatment Options
Treatment Options Under Clinical Evaluation
Current Clinical Trials

Only a small number of children and adolescents with extracranial germ cell tumors (GCT) relapse as a result of the effectiveness of treatment, though 20% to 30% of patients with advanced-stage extragonadal disease and adolescents with advanced gonadal disease may develop recurrent disease.[1,2] The approach to recurrent disease and its success depend on the initial treatment regimen and on the response of the tumor to treatment.

Boys with stage I testicular disease originally treated with surgical resection and observation can usually be salvaged, if relapse occurs, by further surgical excision and standard cisplatin, etoposide and bleomycin (PEB) or carboplatin, etoposide, and bleomycin (JEB) chemotherapy.[3,4] Several European studies also have reported encouraging salvage rates for stage I ovarian GCT patients originally treated with surgery and observation.[5,6]

Most children with recurrent sacrococcygeal tumors will recur locally at the primary tumor site. For these children, complete surgical resection of the recurrent tumor and the coccyx is the basis of salvage treatment; preoperative chemotherapy may assist the surgical resection. In patients in whom a complete salvage resection is not achieved, postoperative local irradiation should be considered.[7]

Despite overall cure rates greater than 80%, children with extracranial germ cell tumors who have disease recurrence after surgery and three-agent platinum-based combination chemotherapy (PEB or JEB) have an unfavorable prognosis. Reports regarding the treatment and outcome of these children include small patient samples.[7] Reports of salvage treatment strategies used in adult recurrent germ cell tumors include larger numbers of patients, but the differences between children and adults regarding the location of the primary germ cell tumor site, pattern of relapse, and the biology of childhood germ cell tumors may limit the applicability of adult salvage approaches to children.[8]

In adults with recurrent GCT, several chemotherapy combinations have achieved relatively good disease-free status.[9] A combination of paclitaxel and gemcitabine has demonstrated activity in adults with testicular GCT who have relapsed after high-dose (HD) chemotherapy and hematopoietic stem cell transplant (SCT).[10]

HD chemotherapy with autologous stem cell rescue has been explored in adults with recurrent testicular GCT. HD-chemotherapy plus hematopoietic stem cell rescue has been reported to cure adult patients with relapsed testicular GCT, even as third-line therapy and in cisplatin-refractory patients.[11] While several other studies support this approach, [12,13,10,14]others do not. [15,16] Salvage attempts using HD-chemotherapy regimens may be of little benefit if the patient is not clinically disease free at the time hematopoietic SCT.[11,17]

The role of HD-chemotherapy and hematopoietic stem cell rescue for recurrent pediatric GCT is not established, despite anecdotal reports. In one European series, ten of 23 children with relapsed extragonadal GCT achieved long-term (median follow-up 66 months) disease-free survival by using HD-chemotherapy with stem cell support.[18] Further study is needed in children and adolescents.

There are no standard treatment options for recurrent pediatric GCT. The role for surgery in selected patients who have recurrent GCT has not been established but should be considered.

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• AGCT0521: Though a standard pediatric salvage approach does not exist, the COG trial, AGCT0521, is for children with relapsed GCT. The trial will include the use of paclitaxel, ifosfamide, and carboplatin.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent childhood malignant 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

1. Mann JR, Raafat F, Robinson K, et al.: The United Kingdom Children's Cancer Study Group's second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol 18 (22): 3809-18, 2000.  [PUBMED Abstract]
   
   
2. Cushing B, Giller R, Cullen JW, et al.: Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study--Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol 22 (13): 2691-700, 2004.  [PUBMED Abstract]
   
   
3. Schlatter M, Rescorla F, Giller R, et al.: Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children's Cancer Group/Pediatric Oncology Group. J Pediatr Surg 38 (3): 319-24; discussion 319-24, 2003.  [PUBMED Abstract]
   
   
4. Rogers PC, Olson TA, Cullen JW, et al.: Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891. J Clin Oncol 22 (17): 3563-9, 2004.  [PUBMED Abstract]
   
   
5. Baranzelli MC, Bouffet E, Quintana E, et al.: Non-seminomatous ovarian germ cell tumours in children. Eur J Cancer 36 (3): 376-83, 2000.  [PUBMED Abstract]
   
   
6. Dark GG, Bower M, Newlands ES, et al.: Surveillance policy for stage I ovarian germ cell tumors. J Clin Oncol 15 (2): 620-4, 1997.  [PUBMED Abstract]
   
   
7. Schneider DT, Wessalowski R, Calaminus G, et al.: Treatment of recurrent malignant sacrococcygeal germ cell tumors: analysis of 22 patients registered in the German protocols MAKEI 83/86, 89, and 96. J Clin Oncol 19 (7): 1951-60, 2001.  [PUBMED Abstract]
   
   
8. Nichols CR: Treatment of recurrent germ cell tumors. Semin Surg Oncol 17 (4): 268-74, 1999.  [PUBMED Abstract]
   
   
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 16 (7): 2500-4, 1998.  [PUBMED Abstract]
   
   
10. Einhorn LH, Brames MJ, Juliar B, et al.: 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 25 (5): 513-6, 2007.  [PUBMED Abstract]
    
    
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 357 (4): 340-8, 2007.  [PUBMED Abstract]
    
    
12. 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]
    
    
13. Motzer RJ, Mazumdar M, Sheinfeld J, et al.: Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients. J Clin Oncol 18 (6): 1173-80, 2000.  [PUBMED Abstract]
    
    
14. Rick O, Bokemeyer C, Beyer J, et al.: Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer. J Clin Oncol 19 (1): 81-8, 2001.  [PUBMED Abstract]
    
    
15. Beyer J, Rick O, Siegert W, et al.: Salvage chemotherapy in relapsed germ cell tumors. World J Urol 19 (2): 90-3, 2001.  [PUBMED Abstract]
    
    
16. 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]
    
    
17. Rick O, Bokemeyer C, Weinknecht S, et al.: Residual tumor resection after high-dose chemotherapy in patients with relapsed or refractory germ cell cancer. J Clin Oncol 22 (18): 3713-9, 2004.  [PUBMED Abstract]
    
    
18. De Giorgi U, Rosti G, Slavin S, et al.: Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours. Br J Cancer 93 (4): 412-7, 2005.  [PUBMED Abstract]
    
    

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