Table 1.

Therapeutic trials for children with medulloblastoma

Trial	Target population	Approach/Drugs	Outcomes
SIOP PNET-3 85	> 3 years of age with low-risk (M1/M0) disease	Vincristine, etoposide, carboplatin, and cyclophosphamide followed by radiation versus radiation alone	Chemotherapy + Radiation - 3-year EFS 79% - 5-year EFS 74% Radiation alone - 3-year EFS 65% - 5-year EFS 60%
SFOP 86	< 5 years of age with newly diagnosed, maximally resected disease	Carboplatin, procarbazine, etoposide, cisplatin, vincristine, and cyclophosphamide over 7 cycles Salvage with busulfan and thiotepa, second-look surgery, and radiation at time of local relapse versus melphalan, busulfan, and thiotepa with autologous stem cell rescue plus focal radiation for recurrent focal disease or melphalan, cisplatin, thiotepa with autologous stem cell rescue and reduced-dose CSI for recurrent, metastatic disease	Demonstrated cure without radiation possible in patients with focal disease who underwent gross total resection and those with local recurrence could be salvaged by combined chemotherapy and radiation
HIT SKK ‘87 60	< 3 years of age	HIT SKK ‘87 Postoperative arms determined by standard or high-risk disease Low risk: Procarbazine, vincristine, high-dose methotrexate High risk: Procarbazine, ifosfamide, etoposide, high-dose methotrexate, cisplatin, cyclophosphamide Radiation at 3 years of age or time of progression	Chemotherapy can prolong time to radiation or allows potential complete avoidance of radiation in patients with focal disease who achieved gross total resection Children without macroscopic metastases (complete resection): - 10-year PFS 53% - 10-year OS 59% Children without macroscopic metastases (incomplete resection): - 10-year PFS 56% - 10-year OS 67% Children with metastases: - 10-year PFS 33% - 10-year OS 44%
HIT SKK ‘91 84		Arm 1—Neoadjuvant chemotherapy (Ifosfamide, etoposide, high-dose methotrexate, cisplatin, cytarabine x 2 cycles) before radiation Arm 2—Postoperative radiation with concomitant vincristine followed by cisplatin, lomustine, and vincristine x 8 cycles	Maintenance chemotherapy most effective in patients 6 years or older with low-risk disease, otherwise no statistically significant differences between arms
HIT SKK ‘92 pilot 59	< 3 years of age	Postoperative cyclophosphamide, methotrexate, vincristine, carboplatin, and etoposide with intraventricular methotrexate Radiation only if residual disease and >18 months of age at end of chemotherapy	Children without macroscopic metastases (complete resection): - 5-year PFS 93% - 5-year OS 100% Children without macroscopic metastases (incomplete resection): - 5-year PFS 43% - 5-year OS 56% Children with macroscopic metastases: - 5-year PFS 36% - 5-year OS 40% Children with ND MB: - 10-year PF 89% - 10-year OS 89%
Head Start I & II 65	< 3 years of age	Induction with vincristine, cisplatin, cyclophosphamide, and etoposide x 5 cycles Consolidation with myeloablative chemotherapy with carboplatin, thiotepa and autologous stem cell transplant (Doses varied between Head Start I & II)	Children without macroscopic metastases (complete resection): - 5-year PFS 52% - 5-year OS 79% Children without macroscopic metastases (incomplete resection): - 5-year PFS 64% - 5-year OS 57% Children with ND MB: - 5-year PF 67% - 5-year OS 78%
COG 99703 64	6 months to 3 years of age	Induction with cisplatin, vincristine, cyclophosphamide, and etoposide x 3 cycles Consolidation with high-dose carboplatin and thiotepa followed by autologous stem cell transplant x 3 cycles	- 5-year EFS 44% - 5-year OS 64% Children with ND MB: - 5-year OS 85%
CCG 9921 98,99	< 3 years of age	Induction vincristine, cisplatin, cyclophosphamide, and etoposide alternating with vincristine, carboplatin, ifosfamide, and etoposide Maintenance vincristine, etoposide, and cyclophosphamide No radiation unless residual tumor after induction or metastatic disease at diagnosis	- 5-year EFS 32% - 5-year OS 43% Children with ND MB: - 5-year EFS 77% - 5-year OS 85%
COG P9934 100	8 months to 3 years of age	Induction with cyclophosphamide, vincristine, cisplatin, and etoposide followed by age- and response-adjusted radiation, if no progression Maintenance with cyclophosphamide, vincristine, and oral etoposide	- 4-year EFS 50% - 4-year OS 69% Children with ND MB: - 4-year EFS 58%
COG 9961 79	3 years to 21 years of age	Randomized to postradiation cisplatin and vincristine plus either CCNU or cyclophosphamide	- 5-year EFS 81% - 5-year OS 87% No impact of chemotherapy choice

Abbreviations: EFS, event-free survival; OS, overall survival; PFS, progression-free survival; ND MB, nodular/desmoplastic medulloblastoma.