A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group.

Abstract

BACKGROUND:

Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy.

PROCEDURE:

Patients enrolled in the study had high-risk disease defined as ≥1.5 cm2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m2 per day (treatment 1), which was reduced to 35 mg/m2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine.

RESULTS:

Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072).

CONCLUSIONS:

Oral etoposide was tolerable at 35 mg/m2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data.

• Authors: Adam J Esbenshade, Mehmet Kocak, Linda Hershon, Pierre Rousseau, Jean-Claude Decarie, Susan Shaw, Peter Burger, Henry S Friedman, Amar Gajjar, Albert Moghrabi
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 64 Issue 6 (06 2017) ISSN: 1545-5017 [Electronic] United States
• PMID: 28000417 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Etoposide

Topics

• Administration, Oral
• Adolescent
• Adult
• Chemoradiotherapy, Adjuvant
• Child
• Child, Preschool
• Disease-Free Survival
• Etoposide (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Male
• Medulloblastoma (diagnosis, mortality, therapy)
• Risk Factors
• Survival Rate