Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors

Shakeel Modak, Sharon Gardner, Ira J. Dunkel, Casilda Balmaceda, Marc K. Rosenblum, Douglas C. Miller, Steven Halpern, Jonathan L. Finlay

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1934-1943
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number10
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

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Thiotepa
Germ Cell and Embryonal Neoplasms
Stem Cells
Drug Therapy
Germinoma
Survival
Disease-Free Survival
Pulmonary Fibrosis
Poisons
Tumor Burden

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Modak, S., Gardner, S., Dunkel, I. J., Balmaceda, C., Rosenblum, M. K., Miller, D. C., ... Finlay, J. L. (2004). Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. Journal of Clinical Oncology, 22(10), 1934-1943. https://doi.org/10.1200/JCO.2004.11.053
Modak, Shakeel ; Gardner, Sharon ; Dunkel, Ira J. ; Balmaceda, Casilda ; Rosenblum, Marc K. ; Miller, Douglas C. ; Halpern, Steven ; Finlay, Jonathan L. / Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 10. pp. 1934-1943.
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abstract = "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.",
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Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. / Modak, Shakeel; Gardner, Sharon; Dunkel, Ira J.; Balmaceda, Casilda; Rosenblum, Marc K.; Miller, Douglas C.; Halpern, Steven; Finlay, Jonathan L.

In: Journal of Clinical Oncology, Vol. 22, No. 10, 01.12.2004, p. 1934-1943.

Research output: Contribution to journalArticle

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T1 - Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors

AU - Modak, Shakeel

AU - Gardner, Sharon

AU - Dunkel, Ira J.

AU - Balmaceda, Casilda

AU - Rosenblum, Marc K.

AU - Miller, Douglas C.

AU - Halpern, Steven

AU - Finlay, Jonathan L.

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N2 - 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.

AB - 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.

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