Abstract
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.
Highlights
We utilised only randomised clincial trials of first line chemotherapy for advanced ovarian cancer patients published in the English language and in complete form between 1975 and 1989 inclusive
Trials were not included in this analysis if (a) they were preliminary reports; (b) they were phase I or phase II; (c) if more than 15% of the patients were previously treated with chemotherapy; or (d) if more than 15% of the patients were stage I or II
Examination of the relationship between response and total dose intensity was performed using the regression model defined in the Methods section
Summary
We utilised only randomised clincial trials of first line chemotherapy for advanced ovarian cancer patients published in the English language and in complete form between 1975 and 1989 inclusive. Trials were not included in this analysis if (a) they were preliminary reports; (b) they were phase I or phase II; (c) if more than 15% of the patients were previously treated with chemotherapy; or (d) if more than 15% of the patients were stage I or II. Studies with no information about either survival or objective response information were dropped from the analysis. Thirty-two out of 47 initially identified studies were available for analysis of the association between dose intensity and objective response. Twenty-six out of 47 were available for the correlation of dose intensity and survival. Twenty-five of these studies had both objective response and survival information. A complete list of referenced studies is given in the Appendix
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