Phase I clinical trial of valacyclovir and standard of care cyclophosphamide in children with endemic Burkitt lymphoma in Malawi.
Phase I clinical trial of valacyclovir and standard of care cyclophosphamide in children with endemic Burkitt lymphoma in Malawi.
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马拉维特有伯基特淋巴瘤儿童的Valacyclovir和Care环磷酰胺标准的I期临床试验。
DOI：
10.1016/j.clml.2012.11.003
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Shores C
中科院分区：
文献类型：
--
作者：
Olson D;Gulley ML;Tang W;Wokocha C;Mechanic O;Hosseinipour M;Gold SH;Nguluwe N;Mwansambo C;Shores C
由于化疗相关毒性，非洲EB病毒（EBV）相关伯基特淋巴瘤的治疗选择有限。由于其他EB病毒相关疾病对抗病毒药物有反应，我们研究了在马拉维目前的化疗方案中加入抗病毒药物伐昔洛韦。在这个I期安全性研究中，我们发现环磷酰胺联合伐昔洛韦是安全的。现在应该进行II期疗效试验。核苷类似物，包括阿昔洛韦，更昔洛韦，及其前体，已显示出一定的疗效，对几个EB病毒（EBV）相关的疾病，包括活动性EBV感染和移植后淋巴增生性疾病（PTLD）。它们也被提议作为EBV相关恶性肿瘤的可能治疗方法，包括地方性伯基特淋巴瘤。在发展中国家，核苷类似物联合化疗的安全性尚未得到研究，在进行任何大规模疗效试验之前，这是必要的。符合入选标准的3-15岁儿童被分配到一项3+3剂量递增试验，该试验联合伐昔洛韦（15和30 mg/kg，每日3次，持续40天）和环磷酰胺（CPM）（第1天40 mg/kg，第8、18和28天60 mg/kg）或CPM单药治疗。监测受试者的临床和实验室毒性，并定期测量EBV水平。剂量限制性毒性（DLT）是我们的主要结局。我们发现，与CPM单药治疗相比，伐昔洛韦和CPM联合治疗是安全的，不会导致任何DLT。最常见的副作用是呕吐、腹痛和肿瘤部位疼痛，两组相似。具有可测量的血清EBV的患者在其治疗过程中显示出降低的负荷。我们建议II期伐昔洛韦剂量为30 mg/kg，每日3次，持续40天。我们还观察到，12例假定患有伯基特淋巴瘤的患者中有6例在治疗过程中具有可测量的EBV病毒载量，这表明II期研究应进一步研究这种相关性。这项研究为联合伐昔洛韦和CPM治疗地方性伯基特淋巴瘤的II期疗效试验铺平了道路。
Treatment options for Epstein-Barr virus (EBV)-associated Burkitt lymphoma in Africa are limited because of chemotherapy-associated toxicity. Since other EBV-associated diseases respond to antiviral agents, we investigated adding an antiviral agent, valacyclovir, to the current chemotherapy regimen in Malawi. In this phase I safety study, we showed that cyclophosphamide combined with valacyclovir was safe. Phase II efficacy trials should now be undertaken. Nucleoside analogues, including acyclovir, ganciclovir, and their precursors, have shown some efficacy against several Epstein-Barr virus (EBV)-associated diseases, including active EBV infection and posttransplantation lymphoproliferative disorder (PTLD). They have also been proposed as a possible treatment for EBV-associated malignancies, including endemic Burkitt lymphoma. The safety of nucleoside analogues in combination with chemotherapy in the developing world has not been studied and is necessary before any large scale efficacy trials are conducted. Children 3–15 years old meeting inclusion criteria were assigned to a 3+3 dose escalation trial of combination valacyclovir (15 and 30 mg/kg, 3 times daily for 40 days) and cyclophosphamide (CPM) (40 mg/kg day 1, 60 mg/kg on days 8, 18, and 28) or CPM monotherapy. Subjects were monitored for clinical and laboratory toxicity and had EBV levels measured regularly. Dose-limiting toxicity (DLT) was our primary outcome. We found that the combination of valacyclovir and CPM was safe and did not lead to any DLT compared with CPM monotherapy. The most common side effects were vomiting, abdominal pain, and tumor site pain, which were similar in both arms. Patients with measurable serum EBV showed decreased loads over their treatment course. We recommend a phase II valacyclovir dose of 30 mg/kg 3 times daily for 40 days. We also observed that 6 of our 12 patients with presumed Burkitt lymphoma had measurable EBV viral loads that decreased over the course of their treatment, suggesting that phase II studies should investigate this correlation further. This study paves the way for a phase II efficacy trial of combined valacyclovir and CPM in the treatment of endemic Burkitt lymphoma.
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影响因子：
5.4
作者：
Feng, WH;Hong, G;Kenney, SC
通讯作者：
Kenney, SC
影响因子：
158.5
作者：
Calis, Job C. J.;Phiri, Kamija S.;van Hensbroek, Michael Boele
通讯作者：
van Hensbroek, Michael Boele
DOI：
10.1097/qad.0b013e3283437f77
发表时间：
2011-03-13
期刊：
AIDS (London, England)
影响因子：
--
作者：
Achenbach CJ;Cole SR;Kitahata MM;Casper C;Willig JH;Mugavero MJ;Saag MS
通讯作者：
Saag MS
影响因子：
158.5
作者：
Lin, JC;Wang, WY;Jiang, RS
通讯作者：
Jiang, RS
影响因子：
8.8
作者：
Balfour, Henry H., Jr.;Hokanson, Kristin M.;Brundage, Richard C.
通讯作者：
Brundage, Richard C.