Rochford R, Feuer G, Orem J, Banura C, Katongole-Mbidde E, Mwanda W O, Moormann A, Harrington W J, Remick S C
Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
East Afr Med J. 2005 Sep;82(9 Suppl):S155-60. doi: 10.4314/eamj.v82i9.9388.
Strategies to circumvent or lessen the myelotoxicity associated with combination chemotherapy may improve the overall outcome of the management of patients particularly in resource poor settings.
To develop effective non-myelotoxic therapies for Burkitt's Lymphoma (BL) and AIDS-related non-Hodgkin's lymphoma.
Publications, original and review articles, conference abstracts searched mainly on Pubmed indexed for medline.
A systematic review of the clinical problem of combination chemotherapy. Identification of clinical strategies that circumvent or lessen the myelotoxicity of combination cytotoxic chemotherapy. Length of survival, lack of clinically significant (> grade 3) myelosuppression and weight loss were used as markers of myelotoxicity.
Review of published experience with some of these strategies including dose-modification of multi-agent chemotherapy; rationale for targeted therapies, and the preclinical development of a mouse model exploring the role of metronomic scheduling substantiate pragmatism and feasibility of these approaches.
Myelotoxic death rates using multi-agent induction chemotherapy approach 25% for endemic Burkitt's lymphoma and range between 20% to 60% for AIDS-related malignancy. This is mostly explained by the paucity of supportive care compounded by wasting and inanition attributable to advanced cancer and HIV infection making patients more susceptible to myelosuppressive side effects of cytotoxic chemotherapy. Investigations and alternative approaches that lessen or circumvent myelotoxicity of traditional cytotoxic chemotherapy for the management of Burkitt's lymphoma and AIDS-related non-Hodgkin's lymphoma in the resource-constrained setting are warranted. Pertinent pre-clinical and clinical data are emerging to support the need for abrograting the myelosuppressive effects of traditional cytotoxic chemotherapy. This can be achieved by developing targeted anti-viral and other strategies, such as the use of bryostatin 1 and vincristine, and by developing a preclinical mouse model to frame the clinical rationale for a pilot trial of metronomic therapy for the treatment of Burkitt's and AIDS-related lymphoma. Implementation of these investigational approaches must be encouraged as viable anti-cancer therapeutic strategies particularly in the resource-constrained settings.
规避或减轻联合化疗相关骨髓毒性的策略可能会改善患者治疗的总体结果，尤其是在资源匮乏地区。
开发针对伯基特淋巴瘤（BL）和艾滋病相关非霍奇金淋巴瘤的有效非骨髓毒性疗法。
主要在PubMed上检索的出版物、原创和综述文章、会议摘要，这些文献被编入Medline索引。
对联合化疗临床问题的系统评价。确定规避或减轻联合细胞毒性化疗骨髓毒性的临床策略。生存时间、缺乏具有临床意义的（>3级）骨髓抑制和体重减轻被用作骨髓毒性的指标。
回顾这些策略中的一些已发表经验，包括多药化疗的剂量调整；靶向治疗的原理，以及探索节拍给药作用的小鼠模型的临床前开发，证实了这些方法的实用性和可行性。
使用多药诱导化疗方法，地方性伯基特淋巴瘤的骨髓毒性死亡率为25%，艾滋病相关恶性肿瘤的骨髓毒性死亡率在20%至60%之间。这主要是由于支持治疗的匮乏，再加上晚期癌症和艾滋病毒感染导致的消瘦和虚弱，使患者更容易受到细胞毒性化疗骨髓抑制副作用的影响。有必要进行研究并采用替代方法，以减轻或规避传统细胞毒性化疗对资源有限环境中伯基特淋巴瘤和艾滋病相关非霍奇金淋巴瘤的骨髓毒性。相关的临床前和临床数据正在出现，以支持消除传统细胞毒性化疗骨髓抑制作用的必要性。这可以通过开发靶向抗病毒和其他策略来实现，如使用苔藓抑素1和长春新碱，以及开发临床前小鼠模型，为节拍疗法治疗伯基特淋巴瘤和艾滋病相关淋巴瘤的试点试验制定临床依据。必须鼓励实施这些研究方法，将其作为可行的抗癌治疗策略，尤其是在资源有限的环境中。
