Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. (September 2018)

• Record Type: Journal Article
• Authors: Moreno, Lucas; Casanova, Michela; Chisholm, Julia C.; Berlanga, Pablo; Chastagner, Pascal B.; Baruchel, Sylvain; Amoroso, Loredana; Gallego Melcón, Soledad; Gerber, Nicolas U.; Bisogno, Gianni; Fagioli, Franca; Geoerger, Birgit; Glade Bender, Julia L.; Aerts, Isabelle; Bergeron, Christophe; Hingorani, Pooja; Elias, Ileana; Simcock, Mathew; Ferrara, Stefano; Le Bruchec, Yvan; Slepetis, Ruta; Chen, Nianhang; Vassal, Gilles
• Is Part Of: European journal of cancer. Volume 100(2018)
• Page Start: 27
• Page End: 34
• Publication Date: 2018-09
• Subjects: nab-paclitaxel -- Paediatric -- Neuroblastoma -- Rhabdomyosarcoma -- Ewing sarcoma -- Solid tumour; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.05.002
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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. Highlights: This phase 1 study determined the maximum tolerated dose/recommended phase II dose (RP2D) of nab -paclitaxel in paediatric patients. The paediatric RP2D is 240 mg/m 2 given days 1, 8 and 15 every 4 weeks. This dose demonstrated preliminary signs of activity and manageable toxicity. Results warrant the phase II study of nab -paclitaxel in this population.