Phillips K A, Tannock I F
Department of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, Ontario, Canada.
J Clin Oncol. 1998 Sep;16(9):3179-90. doi: 10.1200/JCO.1998.16.9.3179.
To review the features of randomized clinical trials (RCTs) used in the development of agents that may protect against chemotherapy-induced toxicities, including trials of the cardioprotective agent dexrazoxane, hematologic growth factors, and amifostine; to suggest recommendations based on information gained from such trials and improvements in the design of ongoing and future trials.
Critical review of reports of RCTs obtained from a Medline search, references from these articles, and review of trials listed in the physician data query (PDQ) clinical trials data base.
Several of the phase III trials did not use a format of comparing widely accepted strategies of chemotherapy with and without a protective agent. Instead, patients in the control arms of some of the trials have been exposed to more prolonged use or increased dosage of toxic chemotherapy that placed them at greater risk of the toxicity the protective agent was designed to prevent (eg, cardiotoxicity in trials of dexrazoxane, myelosuppression or thrombocytopenia in trials of growth factors).
RCTs have shown clear evidence of biologic activity for the protective agents, but this does not imply therapeutic benefit as compared with alternative strategies such as avoidance of prolonged use of cardiotoxic agents or use of standard doses of chemotherapy. Ongoing and future trials of protective agents should be modified to avoid undue risk to patients.
回顾用于研发可能预防化疗诱导毒性的药物的随机临床试验（RCT）的特点，包括心脏保护剂右丙亚胺、血液学生长因子和氨磷汀的试验；根据从此类试验中获得的信息以及对正在进行和未来试验设计的改进提出建议。
对通过医学文献数据库检索获得的RCT报告、这些文章的参考文献以及医师数据查询（PDQ）临床试验数据库中列出的试验进行批判性回顾。
一些III期试验没有采用比较使用和不使用保护剂的广泛接受的化疗策略的形式。相反，一些试验的对照组患者接触了更长时间的使用或增加剂量的毒性化疗，这使他们面临保护剂旨在预防的毒性的更大风险（例如，右丙亚胺试验中的心脏毒性、生长因子试验中的骨髓抑制或血小板减少）。
RCT已显示出保护剂具有明确的生物学活性证据，但这并不意味着与避免长时间使用心脏毒性药物或使用标准化疗剂量等替代策略相比具有治疗益处。应修改正在进行和未来的保护剂试验，以避免给患者带来不必要的风险。
