TY - JOUR
T1 - Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours
T2 - A collaboration with innovative therapies for children with cancer
AU - Moreno, Lucas
AU - Casanova, Michela
AU - Chisholm, Julia C.
AU - Berlanga, Pablo
AU - Chastagner, Pascal B.
AU - Baruchel, Sylvain
AU - Amoroso, Loredana
AU - Melcón, Soledad Gallego
AU - Gerber, Nicolas U.
AU - Bisogno, Gianni
AU - Fagioli, Franca
AU - Geoerger, Birgit
AU - Glade Bender, Julia L.
AU - Aerts, Isabelle
AU - Bergeron, Christophe
AU - Hingorani, Pooja
AU - Elias, Ileana
AU - Simcock, Mathew
AU - Ferrara, Stefano
AU - Le Bruchec, Yvan
AU - Slepetis, Ruta
AU - Chen, Nianhang
AU - Vassal, Gilles
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Background: nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported. Patients and methods: Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m 2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Results: Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m 2 and grade 4 neutropenia >7 days at 270 mg/m 2 . The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m 2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1–2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m 2 . Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST. Conclusions: nab-Paclitaxel 240 mg/m 2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. ClinicalTrials.gov: NCT01962103. EudraCT: 2013-000144-26.
AB - Background: nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported. Patients and methods: Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m 2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Results: Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m 2 and grade 4 neutropenia >7 days at 270 mg/m 2 . The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m 2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1–2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m 2 . Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST. Conclusions: nab-Paclitaxel 240 mg/m 2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. ClinicalTrials.gov: NCT01962103. EudraCT: 2013-000144-26.
KW - Ewing sarcoma
KW - Neuroblastoma
KW - Paediatric
KW - Rhabdomyosarcoma
KW - Solid tumour
KW - nab-paclitaxel
UR - http://www.scopus.com/inward/record.url?scp=85048796300&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2018.05.002
DO - 10.1016/j.ejca.2018.05.002
M3 - Article
C2 - 29936064
AN - SCOPUS:85048796300
SN - 0959-8049
VL - 100
SP - 27
EP - 34
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -