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Treatment of Recurrent Childhood Malignant GCTs

    Only a small number of children and adolescents with extracranial germ cell tumors (GCTs) relapse.[1,2] However, 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]

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    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 GCTs 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 GCTs include larger numbers of patients, but the differences between children and adults regarding the location of the primary GCT site, pattern of relapse, and the biology of childhood GCTs may limit the applicability of adult salvage approaches to children.

    In adults with recurrent GCTs, several chemotherapy combinations have achieved relatively good disease-free status.[8,9,10,11,12,13] A combination of paclitaxel and gemcitabine has demonstrated activity in adults with testicular GCTs who relapsed after high-dose (HD) chemotherapy and hematopoietic stem cell transplant (SCT).[14]

    HD chemotherapy with autologous stem cell rescue has been explored in adults with recurrent testicular GCTs. HD chemotherapy plus hematopoietic stem cell rescue has been reported to cure adult patients with relapsed testicular GCTs, even as third-line therapy and in cisplatin-refractory patients.[15] While several other studies support this approach,[16,17,14,18,19] others do not.[20,21] Salvage attempts using HD-chemotherapy regimens may be of little benefit if the patient is not clinically disease free at the time of hematopoietic SCT.[15,22]

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