TY - JOUR
T1 - A phase II trial and pharmacokinetic study of oxaliplatin in children with refractory solid tumors
T2 - A Children's Oncology Group study
AU - Beaty, Orren
AU - Berg, Stacey
AU - Blaney, Susan
AU - Malogolowkin, Marcio
AU - Krailo, Mark
AU - Knight, Ronald
AU - Schaiquevich, Paula
AU - Stewart, Clinton
AU - Chen, Zhengjia
AU - Nelson, Marvin
AU - Voss, Stephan
AU - Ivy, S. Percy
AU - Adamson, Peter C.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Background. Platinating agents are used in the treatment of a spectrum of childhood cancers. Oxaliplatin, a third generation platinum compound, may provide less toxicity and be more effective. A phase 2 study was performed to estimate the response rate to single agent oxaliplatin in patients with refractory pediatric solid tumors, and to further describe the toxicities and pharmacokinetics of the drug in this population. Patients and Methods. Subjects, ≤21 years of age at original diagnosis, received oxaliplatin (130 mg/m 2) intravenously every 21 days. Prior platinum exposure was acceptable. Histologies included: Ewing sarcoma/peripheral PNET, osteosarcoma, rhabdomyosarcoma, neuroblastoma, high and low grade astrocytoma, brain stem glioma, ependymoma, hepatoblastoma and selected rare tumors. A two-stage design, enrolling 10+10 subjects, was used for each disease stratum. Limited sampling pharmacokinetic studies were performed. Results. Of 124 eligible subjects (75 males), 113 were evaluable for response and 69 (62%) had received platinum previously. Only one objective response was observed, a partial response in a 6-year-old child with ependymoma. An additional 13 subjects with various other solid tumors had stable disease, receiving a median (range) of 13.5 (2-17) cycles. Five subjects completed 17 treatment cycles. Thrombocytopenia was the most common toxicity observed. The median (range) terminal half-life and clearance for ultrafiltrable platinum were 293 (187-662 hr) and 14.0 (1.9-24.9 L/hr/m2), respectively (n=49). Conclusions. Although reasonably well tolerated, oxaliplatin administered as a single agent has limited activity in pediatric patients with relapsed or refractory solid tumors.
AB - Background. Platinating agents are used in the treatment of a spectrum of childhood cancers. Oxaliplatin, a third generation platinum compound, may provide less toxicity and be more effective. A phase 2 study was performed to estimate the response rate to single agent oxaliplatin in patients with refractory pediatric solid tumors, and to further describe the toxicities and pharmacokinetics of the drug in this population. Patients and Methods. Subjects, ≤21 years of age at original diagnosis, received oxaliplatin (130 mg/m 2) intravenously every 21 days. Prior platinum exposure was acceptable. Histologies included: Ewing sarcoma/peripheral PNET, osteosarcoma, rhabdomyosarcoma, neuroblastoma, high and low grade astrocytoma, brain stem glioma, ependymoma, hepatoblastoma and selected rare tumors. A two-stage design, enrolling 10+10 subjects, was used for each disease stratum. Limited sampling pharmacokinetic studies were performed. Results. Of 124 eligible subjects (75 males), 113 were evaluable for response and 69 (62%) had received platinum previously. Only one objective response was observed, a partial response in a 6-year-old child with ependymoma. An additional 13 subjects with various other solid tumors had stable disease, receiving a median (range) of 13.5 (2-17) cycles. Five subjects completed 17 treatment cycles. Thrombocytopenia was the most common toxicity observed. The median (range) terminal half-life and clearance for ultrafiltrable platinum were 293 (187-662 hr) and 14.0 (1.9-24.9 L/hr/m2), respectively (n=49). Conclusions. Although reasonably well tolerated, oxaliplatin administered as a single agent has limited activity in pediatric patients with relapsed or refractory solid tumors.
KW - Oxaliplatin
KW - Pediatric
KW - Pharmacokinetics
KW - Phase II study
KW - Refractory solid tumor
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U2 - 10.1002/pbc.22544
DO - 10.1002/pbc.22544
M3 - Article
C2 - 20658614
AN - SCOPUS:77955508388
VL - 55
SP - 440
EP - 445
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
SN - 1545-5009
IS - 3
ER -