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 Société Française des Cancers et leucémies de l'Enfant et de l'adolescent (SFCE)

Véronique Minard-Colin, Jean Laurent Ichante, Laurent Nguyen, Angelo Paci, Daniel Orbach, Christophe Bergeron, Anne Sophie Defachelles, Nicolas André, Nadège Corradini, Claudine Schmitt, Marie Dominique Tabone, Pascale Blouin, Nicolas Sirvent, Gisele Goma, Birgit Geoerger, Odile Oberlin

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    Résumé

    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/m2. 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 haemorrhagic 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.

    langue originaleAnglais
    Pages (de - à)2409-2416
    Nombre de pages8
    journalEuropean Journal of Cancer
    Volume48
    Numéro de publication15
    Les DOIs
    étatPublié - 1 oct. 2012

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