The SIOPEL-4 study has demonstrated that dose-dense cisplatin-based chemotherapy dramatically improves outcome in children with high-risk hepatoblastoma in western countries. However, the feasibility and safety of this regimen have not been clarified in Japanese patients.A pilot study, JPLT3-H, was designed to evaluate the safety profile of the SIOPEL-4 regimen in Japanese children with newly diagnosed hepatoblastoma with either metastatic disease or low alpha-fetoprotein.A total of 15 patients (three female) were enrolled. Median age was 2 years (range, 0-14). Three patients were PRETEXT II (where PRETEXT is PRETreatment EXTent of disease), six PRETEXT III, and six PRETEXT IV. All patients had lung metastasis, none had low alpha-fetoprotein. Eight patients completed the prescribed treatment, and seven patients discontinued therapy prematurely, four due to progressive disease and three due to causes other than severe toxicity. Grade 4 neutropenia was documented in most patients in preoperative cycles A1-3 (11/15 in A1, 9/11 in A2, and 7/11 in A3) and in all considering all cycles. Grade 3-4 thrombocytopenia and grade 3 anemia were also frequently observed. Patients experienced several episodes of grade 3 febrile neutropenia, but none had grade 4 febrile neutropenia or severe infections. One patient had grade 3 heart failure only in the first cycle. Other grade 3 or 4 toxicities were hypomagnesemia, anorexia, nausea, mucositis, liver enzyme elevation, fever, infection, and fatigue. There were no unexpected severe toxicities.The toxicity profile of JPLT3-H was comparable to that of SIOPEL-4. Dose-dense cisplatin-based chemotherapy may be feasible among Japanese patients with high-risk hepatoblastoma.
Abstract Medulloblastoma is a type of malignant embryonal tumor in childhood that is considered to require multiagent chemotherapy followed by radical resection and craniospinal irradiation (CSI). However, the outcomes of chemotherapy for this tumor in Japan are unclear. Here, we performed a multicenter retrospective study to determine the prognosis of pediatric medulloblastoma patients in Japan treated with the St. Jude medulloblastoma-96 (SJMB96) regimen. Thirty patients with newly diagnosed medulloblastoma received treatment with the SJMB96 regimen at Juntendo University Hospital in Tokyo (n=10), Saitama Medical University International Medical Center in Saitama (n=10), and Tohoku University Hospital in Miyagi (n=10) from 2011 to 2018. All patients underwent tumor resection and CSI, with radiation doses of 23.4Gy for standard-risk patients (n=11) and 39.6Gy for high-risk patients (n=19). Six weeks after radiation therapy, patients received four cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation according to the SJMB96 regimen. We found that 5-year overall survival was 80.8% among standard-risk patients and 74.2% among high-risk patients. No treatment-related deaths occurred. Eight patients who experienced recurrence died within 80 months of diagnosis. As these treatment outcomes are comparable to those previously reported outside of Japan, our findings indicate that this regimen is a therapeutic option for medulloblastoma patients in Japan.
