Loredana Amoroso1, Victoria Castel2, Gianni Bisogno3, Michela Casanova4, Catalina Marquez-Vega5, Julia C Chisholm6, François Doz7, Lucas Moreno8, Antonio Ruggiero9, Nicolas U Gerber10, Franca Fagioli11, Pooja Hingorani12, Soledad G Melcón13, Ruta Slepetis14, Nianhang Chen14, Yvan le Bruchec15, Mathew Simcock15, Gilles Vassal16. 1. Oncology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy. Electronic address: loredanaamoroso@gaslini.org. 2. Pediatric Hematology/Oncology Unit, University Hospital La Fe, Valencia, Spain. 3. Hematology/Oncology Division, Department of Women's and Children's Health, University of Padova, Padova, Italy. 4. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 5. Hospital Universitario Virgen del Rocío, Seville, Spain. 6. Royal Marsden Hospital, Sutton, UK. 7. Institut Curie and Paris Descartes University, Paris, France. 8. Hospital Infantil Universitario Niño Jesús, Madrid, Spain; Hospital Universitario Vall D'Hebron, Barcelona, Spain. 9. Gemelli Hospital, Catholic University of Rome, Rome, Italy. 10. University Children's Hospital, Zurich, Switzerland. 11. Pediatric Oncology Department, Regina Margherita Children's Hospital, AOU Città della Salute e Della Scienza di Torino, Turin, Italy; Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy. 12. Department of Pediatrics, MD Anderson Cancer Center, Houston, TX, USA. 13. Hospital Universitario Vall D'Hebron, Barcelona, Spain. 14. Bristol-Myers Squibb, Princeton, NJ, USA. 15. Celgene International, A Bristol-Myers Squibb Company, Boudry, Switzerland. 16. Gustave Roussy, Villejuif, France.
Abstract
BACKGROUND: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study. PATIENTS AND METHODS: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m2 of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] + partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR + PR + stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics. RESULTS: Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive. CONCLUSIONS: In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed. TRIAL REGISTRATION: NCT01962103 and EudraCT 2013-000144-26. Published by Elsevier Ltd.
BACKGROUND: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study. PATIENTS AND METHODS: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m2 of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] + partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR + PR + stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics. RESULTS: Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive. CONCLUSIONS: In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed. TRIAL REGISTRATION: NCT01962103 and EudraCT 2013-000144-26. Published by Elsevier Ltd.