TY - JOUR
T1 - Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour
T2 - 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)
AU - Minard-Colin, Véronique
AU - Ichante, Jean Laurent
AU - Nguyen, Laurent
AU - Paci, Angelo
AU - Orbach, Daniel
AU - Bergeron, Christophe
AU - Defachelles, Anne Sophie
AU - André, Nicolas
AU - Corradini, Nadège
AU - Schmitt, Claudine
AU - Tabone, Marie Dominique
AU - Blouin, Pascale
AU - Sirvent, Nicolas
AU - Goma, Gisele
AU - Geoerger, Birgit
AU - Oberlin, Odile
N1 - Funding Information:
Sponsored by the Institut Gustave-Roussy; Partly supported by Société Française des Cancers et leucémies de l’Enfant et de l’adolescent (SFCE), Association Enfants et Santé.
PY - 2012/10/1
Y1 - 2012/10/1
N2 - 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.
AB - 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.
KW - Cyclophosphamide
KW - Metronomic
KW - PK
KW - Phase II
KW - Rhabdomyosarcoma
KW - Vinorelbine
UR - http://www.scopus.com/inward/record.url?scp=84866734818&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2012.04.012
DO - 10.1016/j.ejca.2012.04.012
M3 - Article
C2 - 22633624
AN - SCOPUS:84866734818
SN - 0959-8049
VL - 48
SP - 2409
EP - 2416
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 15
ER -