Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: Good tolerance profile and efficacy in rhabdomyosarcoma - A report from the Societe Francaise des Cancers et leucemies de l'Enfant et de l'adolescent (SFCE)

Aim: This phase II study evaluated efficacy, safety and pharmacokinetics (PK) profile of combination intravenous vinorelbine (VNL) and continuous low doses oral cyclophosphamide (CPM) combination in children and young adults with a recurrent or refractory solid tumour. Methods: A total of 117 patients (median age, 12 years) within six disease strata received intravenous VNL 25 mg/m(2) on days 1, 8, and 15 of each 28-day cycle combined with continuous daily oral CPM 25 mg/m(2). Tumour response was assessed every two cycles according to WHO (World Health Organisation) criteria. PK of VNL was investigated in a subset of 18 patients aged 4-15 years. Results: In rhabdomyosarcoma (RMS) (n = 50), the best overall response rate (ORR) was 36% with four complete (8%) and 14 partial responses (28%). The best ORR was 13% in Ewing's sarcoma (n = 15), 6% in non-RMS soft tissue sarcoma (n = 16), and 6% in neuroblastoma (n = 16). No response was observed in osteosarcoma (n = 10) and medulloblastoma (n = 7). The main grade 3/4 toxicity was neutropenia (38%). Other severe toxicities were limited with 3% of peripheral neuropathy and no hemorrhagic cystitis. The PK analysis revealed equivalent blood exposure to VNL between children >4 years and adult series when the VNL dose was based on the body surface area-based dosing. Concluding statement: In heavily pre-treated children, VNL combined with CPM showed an interesting response rate in RMS and an acceptable toxicity profile supporting further evaluation of these agents in phase III trials. (C) 2012 Elsevier Ltd. All rights reserved.