Alberto Garaventa1, Ulrike Poetschger2, Dominique Valteau-Couanet3, Roberto Luksch4, Victoria Castel5, Martin Elliott6, Shifra Ash7, Godfrey C F Chan8, Geneviève Laureys9, Maja Beck-Popovic10, Kim Vettenranta11, Walentyna Balwierz12, Henrik Schroeder13, Cormac Owens14, Maja Cesen15, Vassilios Papadakis16, Toby Trahair17, Gudrun Schleiermacher18, Peter Ambros2, Stefania Sorrentino1, Andrew D J Pearson19, Ruth Lydia Ladenstein20. 1. IRCCS Istituto Giannina Gaslini, Genova, Italy. 2. Children's Cancer Research Institute, Vienna, Austria. 3. Gustave Roussy, Villejuif, Paris, France. 4. Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 5. Pediatric Oncology Unit, Hospital Universitari I Politecnic La Fe, Valencia, Spain. 6. Leeds Teaching Hospitals, NHS Trust, Leeds, United Kingdom. 7. Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel. 8. University of Hong Kong and Hong Kong Children's Hospital, Hong Kong SAR, China. 9. University Hospital Ghent, Ghent, Belgium. 10. University Hospital Lausanne, Switzerland. 11. Children's Hospital, University of Helsinki, Helsinki, Finland. 12. Jagiellonian University Medical College, Krakow, Poland. 13. Department of Paediatrics, University Hospital of Aarhus, Denmark. 14. University of Dublin, Ireland. 15. Pediatric Clinic, Ljubljana, Slovenia. 16. Agia Sofia Children's Hospital, Athens, Greece. 17. Sydney Children's Hospital, Randwick, Australia. 18. Institut Curie, Paris, France. 19. Retired. Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom. 20. Department of Paediatrics, St Anna Children's Hospital and Children's Cancer Research Institute, Medical University, Vienna, Austria.
Abstract
PURPOSE: Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). PATIENTS AND METHODS: Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. RESULTS: A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n = 313) or MSKCC-N5 (n = 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 (P = .368), and 3-year EFS was 44% ± 3% for rCOJEC compared with 47% ± 3% for MSKCC-N5 (P = .527). Three-year overall survival was 60% ± 3% for rCOJEC compared with 65% ± 3% for MSKCC-N5 (P = .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) (P < .001); infection 35% versus 25% (P = .011); stomatitis 25% versus 3% (P < .001); nausea and vomiting 17% versus 7% (P < .001); and diarrhea 7% versus 3% (P = .011). CONCLUSION: No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.
PURPOSE: Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). PATIENTS AND METHODS: Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. RESULTS: A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n = 313) or MSKCC-N5 (n = 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 (P = .368), and 3-year EFS was 44% ± 3% for rCOJEC compared with 47% ± 3% for MSKCC-N5 (P = .527). Three-year overall survival was 60% ± 3% for rCOJEC compared with 65% ± 3% for MSKCC-N5 (P = .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) (P < .001); infection 35% versus 25% (P = .011); stomatitis 25% versus 3% (P < .001); nausea and vomiting 17% versus 7% (P < .001); and diarrhea 7% versus 3% (P = .011). CONCLUSION: No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.
Authors: Wayne L Furman; Beth McCarville; Barry L Shulkin; Andrew Davidoff; Matthew Krasin; Chia-Wei Hsu; Haitao Pan; Jianrong Wu; Rachel Brennan; Michael W Bishop; Sara Helmig; Elizabeth Stewart; Fariba Navid; Brandon Triplett; Victor Santana; Teresa Santiago; Jacquelyn A Hank; Stephen D Gillies; Alice Yu; Paul M Sondel; Wing H Leung; Alberto Pappo; Sara M Federico Journal: J Clin Oncol Date: 2021-12-06 Impact factor: 44.544
Authors: Angela Bellini; Ulrike Pötschger; Virginie Bernard; Eve Lapouble; Sylvain Baulande; Peter F Ambros; Nathalie Auger; Klaus Beiske; Marie Bernkopf; David R Betts; Jaydutt Bhalshankar; Nick Bown; Katleen de Preter; Nathalie Clément; Valérie Combaret; Jaime Font de Mora; Sally L George; Irene Jiménez; Marta Jeison; Barbara Marques; Tommy Martinsson; Katia Mazzocco; Martina Morini; Annick Mühlethaler-Mottet; Rosa Noguera; Gaelle Pierron; Maria Rossing; Sabine Taschner-Mandl; Nadine Van Roy; Ales Vicha; Louis Chesler; Walentyna Balwierz; Victoria Castel; Martin Elliott; Per Kogner; Geneviève Laureys; Roberto Luksch; Josef Malis; Maja Popovic-Beck; Shifra Ash; Olivier Delattre; Dominique Valteau-Couanet; Deborah A Tweddle; Ruth Ladenstein; Gudrun Schleiermacher Journal: J Clin Oncol Date: 2021-06-11 Impact factor: 50.717