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Thiotepa-Based High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Patients With Recurrent or Progressive CNS Germ Cell Tumors

From the Departments of Pediatrics and Pathology, Memorial Sloan-Kettering Cancer Center; Department of Neurology, Columbia University; and the Departments of Pediatrics and Pathology, New York University Medical Center, New York, NY.

Address reprint requests to Shakeel Modak, MD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: modaks{at}mskcc.org

PURPOSE: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs).

PATIENTS AND METHODS: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR.

RESULTS: Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% ± 12% and 52% ± 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P = .016 and .014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P < .001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC.

CONCLUSION: Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.

Presented in part at the First International Symposium on CNS Germ Cell Tumors, September 17-19, 2003, Kyoto, Japan.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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