Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors

Jan Craig Buckner, Prema P. Peethambaram, William A. Smithson, Robert V. Groover, Paula J. Schomberg, David W. Kimmel, Corey Raffel, Judith R. O'Fallon, Joseph Neglia, Edward G. Shaw

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Abstract

Purpose: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagnosed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. Patients and Methods: Seventeen patients aged 8 to 24 years with histologically proven CNS GCT received etoposide (100 mg/m2/d) plus cisplatin (20 mg/m2/d) daily for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine patients had germinomas; eight had mixed GCT. Four patients (three with germinomas and one with mixed GCT) presented with leptomeningeal dissemination. Results: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial regression before radiation. Six of seven assessable patients with elevated CSF levels of alpha-fetoprotein or beta-human chorionic gonadotropin had normalization with chemotherapy alone; all normalized with combined chemotherapy and radiation therapy. All 17 patients are alive without evidence of disease (median follow-up, 51 months). One patient developed a relapse in the spinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring surgery. Thus far, only minimal long- term deterioration in neurocognitive function has been detected as a consequence of protocol treatment. Conclusion: Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.

Original languageEnglish (US)
Pages (from-to)933-940
Number of pages8
JournalJournal of Clinical Oncology
Volume17
Issue number3
StatePublished - Mar 1999

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Germ Cell and Embryonal Neoplasms
Radiation
Drug Therapy
Etoposide
Germinoma
Cisplatin
Radiotherapy
Spinal Diseases
Carotid Stenosis
alpha-Fetoproteins
Chorionic Gonadotropin
Clinical Protocols
Disease-Free Survival
Histology
Survival Rate
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Buckner, J. C., Peethambaram, P. P., Smithson, W. A., Groover, R. V., Schomberg, P. J., Kimmel, D. W., ... Shaw, E. G. (1999). Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. Journal of Clinical Oncology, 17(3), 933-940.

Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. / Buckner, Jan Craig; Peethambaram, Prema P.; Smithson, William A.; Groover, Robert V.; Schomberg, Paula J.; Kimmel, David W.; Raffel, Corey; O'Fallon, Judith R.; Neglia, Joseph; Shaw, Edward G.

In: Journal of Clinical Oncology, Vol. 17, No. 3, 03.1999, p. 933-940.

Research output: Contribution to journalArticle

Buckner, JC, Peethambaram, PP, Smithson, WA, Groover, RV, Schomberg, PJ, Kimmel, DW, Raffel, C, O'Fallon, JR, Neglia, J & Shaw, EG 1999, 'Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors', Journal of Clinical Oncology, vol. 17, no. 3, pp. 933-940.
Buckner JC, Peethambaram PP, Smithson WA, Groover RV, Schomberg PJ, Kimmel DW et al. Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. Journal of Clinical Oncology. 1999 Mar;17(3):933-940.
Buckner, Jan Craig ; Peethambaram, Prema P. ; Smithson, William A. ; Groover, Robert V. ; Schomberg, Paula J. ; Kimmel, David W. ; Raffel, Corey ; O'Fallon, Judith R. ; Neglia, Joseph ; Shaw, Edward G. / Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 3. pp. 933-940.
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AU - Buckner, Jan Craig

AU - Peethambaram, Prema P.

AU - Smithson, William A.

AU - Groover, Robert V.

AU - Schomberg, Paula J.

AU - Kimmel, David W.

AU - Raffel, Corey

AU - O'Fallon, Judith R.

AU - Neglia, Joseph

AU - Shaw, Edward G.

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N2 - Purpose: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagnosed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. Patients and Methods: Seventeen patients aged 8 to 24 years with histologically proven CNS GCT received etoposide (100 mg/m2/d) plus cisplatin (20 mg/m2/d) daily for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine patients had germinomas; eight had mixed GCT. Four patients (three with germinomas and one with mixed GCT) presented with leptomeningeal dissemination. Results: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial regression before radiation. Six of seven assessable patients with elevated CSF levels of alpha-fetoprotein or beta-human chorionic gonadotropin had normalization with chemotherapy alone; all normalized with combined chemotherapy and radiation therapy. All 17 patients are alive without evidence of disease (median follow-up, 51 months). One patient developed a relapse in the spinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring surgery. Thus far, only minimal long- term deterioration in neurocognitive function has been detected as a consequence of protocol treatment. Conclusion: Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.

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