Carboplatin-based primary chemotherapy for infants and young children with CNS tumors.

Abstract

BACKGROUND:

A carboplatin-based chemotherapy regimen was used as primary postoperative therapy in infants with central nervous system (CNS) tumors to limit renal and ototoxicity and to target systemic exposure.

METHODS:

Fifty-three patients aged <age 3 years with embryonal CNS tumor medulloblastoma (n = 20), ependymoma (EP, n = 21), choroid plexus carcinoma (CPCA, n = 5), and primitive embryonal neoplasms including atypical teratoid rhabdoid tumors (n = 7) were treated with cyclophosphamide, etoposide, and carboplatin. Radiation therapy was used only for residual disease at the end of chemotherapy or disease progression.

RESULTS:

The response rate after 2 cycles of chemotherapy was 34% (complete response, 13.8%; partial response, 20.7%). Myelosuppression was the dominant toxicity; 2 patients had toxic deaths related to thrombocytopenia with trauma. The 5-year overall survival (OS) was 49% +/- 7%, and the progression-free survival (PFS) was 31% +/- 7%, with a median follow-up of 11.4 years (range, 5.2-15.0 years). For medulloblastoma, the 5-year PFS was 26% +/- 9%; for EP it was 33% +/- 10%; for CPCA it was 80% +/- 18%; and for primitive neuroectodermal and atypical teratoid rhabdoid tumors it was 0%. Localized EP patients with gross total resection who did not undergo radiotherapy had a 5-year PFS of 57% +/- 17% and OS of 71% +/- 16%. Two patients developed late second malignancies; 1 was associated with germline p53 mutation.

CONCLUSIONS:

The results confirm that carboplatin has similar activity to cisplatin in otherwise similar regimens. Five-year survival data are comparable to those reported in other recent studies, including high-dose chemotherapy studies. Of note is the marked activity in CPCA and gross totally resected EP.

• Authors: Maryam Fouladi, Sri Gururangan, Albert Moghrabi, Peter Phillips, Lindsey Gronewold, Dana Wallace, Robert A Sanford, Amar Gajjar, Larry E Kun, Richard Heideman
• Journal: Cancer (Cancer) Vol. 115 Issue 14 Pg. 3243-53 (Jul 15 2009) ISSN: 0008-543X [Print] United States
• PMID: 19484793 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Etoposide
• Cyclophosphamide
• Carboplatin

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Central Nervous System Neoplasms (drug therapy)
• Chemotherapy, Adjuvant
• Child, Preschool
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Etoposide (administration & dosage)
• Humans
• Infant
• Survival Analysis
• Time Factors
• Treatment Outcome