Torri V, Korn E L, Simon R
Instituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Br J Cancer. 1993 Jan;67(1):190-7. doi: 10.1038/bjc.1993.33.
To determine if chemotherapy dose intensity influences treatment outcome in advanced ovarian cancer, all randomised studies of first line chemotherapy, published between 1975 and 1989, were analysed for relationships between planned dose intensity and (a) objective response and (b) median survival. Total dose intensity of each study regimen was calculated and a weighted regression model providing for systemic differences in response or survival among studies was utilised. Hence, treatment arms of different studies were never directly compared. In addition, relative dose intensities of individual drugs within combinations was similarly evaluated. The improvement in objective response rate when adding one unit of total dose intensity ranged between 12% and 16% depending on baseline response rate. The improvement in median survival when adding one unit of total dose intensity ranged between 2 and 4 months. One unit of total dose intensity corresponds to, for example, 20 mg m2 week of cisplatin, or 25 mg m2 week of doxorubicin, or 350 mg m2 week of cyclophosphamide. The analysis of individual drugs suggested that doxorubicin and the platinum compounds were about equally effective, with cyclophosphamide being less effective. The methodological benefits and limitations of the approach used and the implication of the results are discussed.
为确定化疗剂量强度是否会影响晚期卵巢癌的治疗结果，对1975年至1989年间发表的所有一线化疗随机研究进行了分析，以探讨计划剂量强度与（a）客观缓解率和（b）中位生存期之间的关系。计算了每个研究方案的总剂量强度，并采用了一个考虑研究间反应或生存系统性差异的加权回归模型。因此，不同研究的治疗组从未直接进行比较。此外，还对联合用药中各药物的相对剂量强度进行了类似评估。根据基线缓解率，每增加一个单位的总剂量强度，客观缓解率的提高幅度在12%至16%之间。每增加一个单位的总剂量强度，中位生存期的延长幅度在2至4个月之间。例如，一个单位的总剂量强度相当于顺铂20mg/m²/周，或阿霉素25mg/m²/周，或环磷酰胺350mg/m²/周。对各药物的分析表明，阿霉素和铂类化合物的疗效大致相当，环磷酰胺的疗效稍差。文中讨论了所用方法的优点和局限性以及结果的意义。
