A phase I study of oxaliplatin and doxorubicin in pediatric patients with relapsed or refractory extracranial non-hematopoietic solid tumors.
A phase I study of oxaliplatin and doxorubicin in pediatric patients with relapsed or refractory extracranial non-hematopoietic solid tumors.
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DOI：
10.1002/pbc.24471
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发表时间：
2013-07
影响因子：
3.2
通讯作者：
Venkatramani, Rajkumar
中科院分区：
文献类型：
--
作者：
Mascarenhas, Leo;Malogolowkin, Marcio;Armenian, Saro H.;Sposto, Richard;Venkatramani, Rajkumar
铂类药物和蒽环类药物的组合在儿科实体瘤中显示出活性。本试验评价了奥沙利铂联合多柔比星治疗复发性实体瘤儿科患者的最大耐受剂量（MTD）和剂量限制性毒性（DLT）。每个21天疗程的第1天给予奥沙利铂，第1-3天给予阿霉素。该研究采用标准3 + 3剂量递增设计。评价了三个剂量水平：1）奥沙利铂105 mg/m2和多柔比星20 mg/m2，2）奥沙利铂130 mg/m2和多柔比星20 mg/m2，以及3）奥沙利铂130 mg/m2和多柔比星25 mg/m2。在多柔比星输注前，以10倍多柔比星剂量给予右雷佐生。17例患者入组。剂量水平1为确定的MTD。在剂量水平1的6例患者中有1例观察到2级心脏DLT，在剂量水平2的5例患者中有2例观察到4级血小板减少，在剂量水平3的5例患者中各有1例2级心脏和4级血小板减少。仅在既往暴露于蒽环类药物和胸部放射的患者中观察到心脏DLT。未观察到3级或4级神经毒性或粘膜炎。其中神经母细胞瘤2例，混合性生殖细胞瘤、胸腺神经内分泌癌和鼻咽癌各1例。第1天奥沙利铂105 mg/m2联合第1-3天多柔比星20 mg/m2为MTD。该组合显示出足够的活性，以证明在选择的儿科肿瘤中进行进一步研究的合理性。
The combination of a platinum agent and anthracycline has shown activity in pediatric solid tumors. This trial evaluated the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin combined with doxorubicin in pediatric patients with recurrent solid tumors. Oxaliplatin was administered on day 1 and Doxorubicin on days 1–3 of each 21 day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels were evaluated: 1) oxaliplatin 105 mg/m2 and doxorubicin 20 mg/m2, 2) oxaliplatin 130 mg/m2 and doxorubicin 20 mg/m2, and 3) oxaliplatin 130 mg/m2 and doxorubicin 25 mg/m2. Dexrazoxane was administered at 10 times the doxorubicin dose prior to doxorubicin infusion. Seventeen patients were enrolled. Dose level 1 was the determined MTD. Grade 2 cardiac DLT was seen in 1 of 6 patients on dose level 1, grade 4 thrombocytopenia in 2 of 5 patients on dose level 2, and 1 each of grade 2 cardiac and grade 4 thrombocytopenia in 5 patients on dose level 3. Cardiac DLT was only noted in patients with prior exposure to both anthracycline and chest radiation. No grade 3 or 4 neurotoxicity or mucositis was seen. Objective responses were noted in 2 patients with neuroblastoma and 1 each of mixed germ cell tumor, thymic neuroendocrine carcinoma and nasopharyngeal carcinoma. Oxaliplatin 105 mg/m2 on day 1 combined with doxorubicin 20 mg/m2 days 1–3 was the MTD. This combination shows sufficient activity to justify further studies in select pediatric tumors.
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影响因子：
6.2
作者：
McGregor, Lisa M.;Spunt, Sheri L.;Fouladi, Maryam
通讯作者：
Fouladi, Maryam
影响因子：
6.2
作者：
McGregor, Lisa M.;Spunt, Sheri L.;Blaney, Susan M.
通讯作者：
Blaney, Susan M.
影响因子：
8.8
作者：
Cvitkovic, E
通讯作者：
Cvitkovic, E
影响因子：
3.2
作者：
Beaty, Orren, III;Berg, Stacey;Adamson, Peter C.
通讯作者：
Adamson, Peter C.
影响因子：
45.3
作者：
Geoerger, Birgit;Doz, Francois;Vassal, Gilles
通讯作者：
Vassal, Gilles