Highlights
- •The phase II study confirmed nab-paclitaxel safety/tolerability in pediatric patients.
- •No response was observed in patients with Ewing sarcoma or neuroblastoma.
- •One patient with rhabdomyosarcoma achieved a confirmed partial response.
- •The most common grade III/IV toxicities were neutropenia (50%) and anaemia (48%).
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.
Keywords
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Article info
Publication history
Published online: June 15, 2020
Accepted:
April 23,
2020
Received in revised form:
April 1,
2020
Received:
December 13,
2019
Identification
Copyright
Published by Elsevier Ltd.
