Details

Autor(en) / Beteiligte

• Cohen, Bruce H., MD
• Geyer, J. Russell, MD
• Miller, Douglas C., MD
• Curran, John G., MD
• Zhou, Tianni, PhD
• Holmes, Emi, MS
• Ingles, Sue Ann, PhD
• Dunkel, Ira J., MD
• Hilden, Joanne, MD
• Packer, Roger J., MD
• Pollack, Ian F., MD
• Gajjar, Amar, MD
• Finlay, Jonathan L., MB, ChB

Titel

Pilot Study of Intensive Chemotherapy With Peripheral Hematopoietic Cell Support for Children Less Than 3 Years of Age With Malignant Brain Tumors, the CCG-99703 Phase I/II Study. A Report From the Children's Oncology Group

Ist Teil von

• Pediatric neurology, 2015-07, Vol.53 (1), p.31-46

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Abstract Background The primary goals of the Children's Cancer Group 99703 study were to assess the feasibility and tolerability of—as well as the response rate to—a novel dose-intensive chemotherapy regimen. Methods Between March 1998 and October 2004, 92 eligible patients were enrolled. Following biopsy/resection, patients received three identical cycles of Induction chemotherapy (vincristine, cyclophosphamide, etoposide, and cisplatin) administered every 21-28 days. Patients without tumor progression then received three consolidation cycles of marrow-ablative chemotherapy (thiotepa and carboplatin) followed by autologous hematopoietic cell rescue. Results The maximum tolerated dose of thiotepa was 10 mg/kg/day × 2 days per cycle. The toxic mortality rate was zero during induction and 2.6% during consolidation. Centrally evaluated response rates to induction and consolidation in evaluable patients with residual tumor were 73.3% and 66.7%, respectively. Disease progression rates on induction and consolidation were 4%. Five-year event-free survival and overall survival were 43.9 ± 5.2% and 63.6 ± 5% respectively. Gross total resection versus less than gross total resection were the only significant outcome comparisons: 5-year maximum tolerated dose and overall survival of 54.4 ± 7% versus 28.9 ± 7% ( P  = 0.0065) and 75.9 ± 8% versus 48.7 ± 8% ( P  = 0.0034), respectively. The 5-year maximum tolerated dose for localized (M0) versus metastatic (M1+) medulloblastoma was 67.5 ± 9.5% versus 30 ± 14.5% ( P  = 0.007). The 5-year maximum tolerated dose and overall survival for desmoplastic medulloblastoma patients versus other medulloblastoma were 78.6 ± 11% versus 50.5 ± 12% ( P  = 0.038) and 85.7 ± 9.4% versus 60.6 ± 11.6% ( P  = 0.046), respectively. Conclusions This phase I dose-escalation study of marrow-ablative thiotepa regimen determined a maximum tolerated dose that had acceptable toxicity. Overall survival data justify this strategy for current Children's Oncology Group studies.