Angela Di Giannatale1, Nathalie Dias-Gastellier1, Annick Devos2, Kieran Mc Hugh3, Ariane Boubaker4, Frederic Courbon5, Arnaud Verschuur6, Stéphane Ducassoul7, Katty Malekzadeh1, Michela Casanova8, Loredana Amoroso9, Pascal Chastagner10, Christian M Zwaan2, Caroline Munzer11, Isabelle Aerts12, Judith Landman-Parker13, Riccardo Riccardi14, Marie-Cecile Le Deley1, Birgit Geoerger1, Hervé Rubie15. 1. Institut Gustave Roussy, Université Paris-Sud, 114 Rue Edouard Vaillant, 94805 Villejuif, France. 2. Sophia Children's Hospital/Erasmus MC Rotterdam, 60 Dr. Molewaterplein, 3015 GJ Rotterdam, The Netherlands. 3. Great Ormond Street Hospital, 34 Great Ormond Street, Bloomsbury, London WC1N 3JH, United Kingdom. 4. Centre Hospitalier Universitaire Vaudois, 46 Rue du Bugnon, 1011 Lausanne, Switzerland. 5. Institut Claudius Regaud, 20-24 Rue du pont Saint-Pierre, 31052 Toulouse Cedex, France. 6. Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille Cedex 5, France. 7. Centre Hospitalier Pellegrin Hôpital des Enfants, Place Amélie Raba-Léon, 33076 Bordeaux, France. 8. Fondazione IRCCS Istituto Nazionale Tumori, 1 Via Venezian, 20133 Milano, Italy. 9. Istituto Giannina Gaslini, 5 Via Gerolamo Gaslini, 16147 Genova, Italy. 10. Hôpital Brabois enfants, 5 Allée du Morvan 54511 Nancy, France. 11. Hôpital des Enfants, 330 Avenue de Grande Bretagne, 31059 Toulouse Cedex 9, France. 12. Universita Cattolica, Gemelli, Largo A. Gemelli 8, 00168 Roma, Italy. 13. Institut Curie, 26 Rue d'Ulm, 75248 Paris Cedex 05, France. 14. Hôpital d'Enfants Armand-Trousseau, 26 Avenue du Docteur Arnold Netter, 75571 Paris, France. 15. Hôpital des Enfants, 330 Avenue de Grande Bretagne, 31059 Toulouse Cedex 9, France. Electronic address: rubie.h@chu-toulouse.fr.
Abstract
PURPOSE: To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. PATIENTS AND METHODS: This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150mg/m(2) followed by topotecan at 0.75mg/m(2) intravenously for five consecutive days every 28days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. RESULTS: Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5months. Tumour control rate (complete response (CR)+partial response (PR)+mixed response (MR)+stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. CONCLUSION: Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.
PURPOSE: To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. PATIENTS AND METHODS: This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150mg/m(2) followed by topotecan at 0.75mg/m(2) intravenously for five consecutive days every 28days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. RESULTS: Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5months. Tumour control rate (complete response (CR)+partial response (PR)+mixed response (MR)+stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. CONCLUSION:Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile.
Authors: Rajen Mody; Alice L Yu; Arlene Naranjo; Fan F Zhang; Wendy B London; Barry L Shulkin; Marguerite T Parisi; Sabah-E-Noor Servaes; Mitchell B Diccianni; Jacquelyn A Hank; Mildred Felder; Jennifer Birstler; Paul M Sondel; Shahab Asgharzadeh; Julia Glade-Bender; Howard Katzenstein; John M Maris; Julie R Park; Rochelle Bagatell Journal: J Clin Oncol Date: 2020-04-28 Impact factor: 44.544
Authors: Julie R Park; Rochelle Bagatell; Susan L Cohn; Andrew D Pearson; Judith G Villablanca; Frank Berthold; Susan Burchill; Ariane Boubaker; Kieran McHugh; Jed G Nuchtern; Wendy B London; Nita L Seibel; O Wolf Lindwasser; John M Maris; Penelope Brock; Gudrun Schleiermacher; Ruth Ladenstein; Katherine K Matthay; Dominique Valteau-Couanet Journal: J Clin Oncol Date: 2017-05-04 Impact factor: 44.544
Authors: Loredana Amoroso; Giovanni Erminio; Guy Makin; Andrew D J Pearson; Penelope Brock; Dominique Valteau-Couanet; Victoria Castel; Marlène Pasquet; Genevieve Laureys; Caroline Thomas; Roberto Luksch; Ruth Ladenstein; Riccardo Haupt; Alberto Garaventa Journal: Cancer Res Treat Date: 2017-03-21 Impact factor: 4.679