High-dose chemotherapy for high-risk primary breast cancer: an on-site review of the Bezwoda study

Background The efficacy of high-dose chemotherapy with progenitor-cell resc ue for women with breast cancer is a controversial issue. Although historic ally controlled trials have suggested a survival advantage for high-dose ch emotherapy, several randomised studies have yet to confirm this advantage. Two studies, however, by Bezwoda, of patients with high-risk and metastatic disease, seemed to show a significant survival advantage for high-dose com pared with conventional-dose chemotherapy for metastatic and high-risk prim ary breast cancer. Methods To corroborate the study results before starting a large internatio nal confirmatory study, a US team did an onsite review of records for patie nts in the high-risk study. Limited numbers of records were made available for review, all of which were for patients who received the high-dose-chemo therapy regimen. Findings There was much disparity between the reviewed records and the data presented at two international meetings. In addition, the reviewers saw no signed informed consent, and the institutional review committee had no rec ord of approval for the investigational therapy. After the site visit, Bezw oda admitted scientific misconduct by using a different control chemotherap y regimen from that described in presented data. Interpretation The Bezwoda study should not be used as the basis for furthe r trials to test the efficacy of the cyclophosphamide, mitoxantrone, etopos ide regimen for high-dose chemotherapy in women with high-risk primacy brea st cancer. This review validates the essential nature of on-site audits, es pecially in single-institution studies.