Background: Each of TMZ and VP has been shown its own anti-cancer activity and they have oral formulation. Although there are established active combinations comprising alkylating agent and topoisomerase inhibitor, TMZ and VP combination (TE), has never been evaluated in pediatric solid cancer. We report efficacy, safety, feasibility of outpatient setting of TE in advance of final analysis of rPII. Methods: This multicenter rpII included children and young adults with recurrent or refractory pediatric solid cancer, who received disease-specific standard chemotherapies. The study design has been reported in ASCO2010 (TPS328). TMZ (150 mg/m2) and VP (50 mg/m2) were administered orally on d1-5 and d1-12 respectively every 28 days, repetitively. The main efficacy endpoint, DSMC approved to be published, was response rate. Response was evaluated according to RECIST 1.1 and toxicity was assessed by CTCAE v4.0. Results: Thirty-four patients(pts) from 13 centers, median age 14 years (range 3-30), received TE: 8 neuroblastoma (NB), 5 rhabdomyosarcoma, 6 Ewing sarcoma family tumor, 8 osteosarcoma (OS), 3 CNS tumors and 4 others. Overall 114 cycles were administered (median 3 per patient; range 1-20). Seventeen pts experienced grade 3-4 neutropenia, but none developed febrile neutropenia. Eight pts had grade 3-4 thrombocytopenia and twelve pts developed grade 3-4 anemia. No grade 4 non-hematological toxicity occurred. Hospitalization was required only in two pts due to VZV infection and grade 2 fever episode, respectively. Response rate (RR) was 14.7% with CR 1 and PR4. Disease control rate (CR+PR+ more than two courses stable disease (SD)) was 38.2% with eight SD. Clinical benefit ratio (CBR, CR+PR+long SD) was 29.4% with five long SD (stable disease during more than 4 course). In NB, CBR was 62.5% with 1 CR, 1 PR and 3 long SD. In OS, RR was 40.7% with 3 PR/7 (one who terminated therapy first 2-3 days due to tumor hemorrhage was excluded). Conclusions: TE is a promising regimen for heavily pretreated recurrent pediatric solid cancer, especially in NB and OS, with acceptable toxicities in outpatient setting. Clinical trial information: 000003002.