Phase II results from a phase I/II study to assess the safety and efficacy of weekly nab-paclitaxel in paediatric patients with recurrent or refractory solid tumours: A collaboration with the European Innovative Therapies for Children with Cancer Network

Loredana Amoroso, Victoria Castel, Gianni Bisogno, Michela Casanova, Catalina Marquez-Vega, Julia C Chisholm, François Doz, Lucas Moreno, Antonio Ruggiero, Nicolas U Gerber, Franca Fagioli, Pooja Hingorani, Soledad G Melcón, Ruta Slepetis, Nianhang Chen, Yvan le Bruchec, Mathew Simcock, Gilles Vassal

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalEur. J. Cancer
Volume135
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Adolescent
  • Age Factors
  • Albumins/administration & dosage
  • Antineoplastic Agents, Phytogenic/administration & dosage
  • Bone Neoplasms/drug therapy
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Europe
  • Female
  • Humans
  • Infant
  • Male
  • Neuroblastoma/drug therapy
  • Paclitaxel/administration & dosage
  • Progression-Free Survival
  • Rhabdomyosarcoma/drug therapy
  • Sarcoma, Ewing/drug therapy
  • Time Factors
  • Tissue Distribution
  • Young Adult

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