Ahmad A Al-Hader1, Amit Jain, Nawar Al-Nasrallah, Lawrence H Einhorn. 1. *Division of Hematology/Oncology, Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN †Talahassee Memorial Healthcare, Tallahassee, FL.
Abstract
BACKGROUND: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin-based chemotherapy. Postchemotherapy teratoma can usually be surgically resected. However, teratoma, which is pluripotent tissue, can undergo malignant transformation along mesodermal elements to primitive neuroectodermal tumor (PNET). Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with malignant transformation to PNET with cyclophosphamide+doxorubicin+vincristine (CAV) alternating with ifosfamide+etoposide (IE). METHODS: We reviewed 86 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2012. We identified 18 patients who were treated with chemotherapy comprising cyclophosphamide (1000 to 1200 mg/m), doxorubicin (50 to 75 mg/m), and vincristine (2 mg) alternating with ifosfamide (1.8 g/m) plus etoposide (100 mg/m) for 5 consecutive days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoietic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. RESULTS: Twelve patients had unresectable disease and 6 were treated in an adjuvant setting. Median age was 29 years (range, 20 to 53 y). Nine of the 12 metastatic patients achieved objective response by RECIST criteria. Six of those were rendered with no evidence of disease (NED) with further surgery. Although 4 of the 6 patients subsequently relapsed, 1 patient remains alive and NED at 78 months. The 6 patients who received adjuvant treatment are alive with NED at 9 to 90 months with a median duration of 32.7 months. CONCLUSIONS: CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long-term disease-free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.
BACKGROUND: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin-based chemotherapy. Postchemotherapy teratoma can usually be surgically resected. However, teratoma, which is pluripotent tissue, can undergo malignant transformation along mesodermal elements to primitive neuroectodermal tumor (PNET). Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with malignant transformation to PNET with cyclophosphamide+doxorubicin+vincristine (CAV) alternating with ifosfamide+etoposide (IE). METHODS: We reviewed 86 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2012. We identified 18 patients who were treated with chemotherapy comprising cyclophosphamide (1000 to 1200 mg/m), doxorubicin (50 to 75 mg/m), and vincristine (2 mg) alternating with ifosfamide (1.8 g/m) plus etoposide (100 mg/m) for 5 consecutive days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoietic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. RESULTS: Twelve patients had unresectable disease and 6 were treated in an adjuvant setting. Median age was 29 years (range, 20 to 53 y). Nine of the 12 metastatic patients achieved objective response by RECIST criteria. Six of those were rendered with no evidence of disease (NED) with further surgery. Although 4 of the 6 patients subsequently relapsed, 1 patient remains alive and NED at 78 months. The 6 patients who received adjuvant treatment are alive with NED at 9 to 90 months with a median duration of 32.7 months. CONCLUSIONS:CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long-term disease-free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.
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