Up front tandem high-dose chemotherapy (HD) compared to standard chemotherapy with doxorubicin and paclitaxel (AT) in metastatic breast cancer (MBC): Final results of a randomized trial

Abstract

641 Background: Trials with late intensification HD have failed to show an advantage in overall survival (OS) for patients with MBC. This trial was initiated to compare up front tandem HD with cyclophosphamide, mitoxantrone and etoposide or standard-dose therapy with AT in patients with MBC. Methods: Between 04/98 and 02/02, 93 pts below 60 ys of age without prior chemotherapy for metastatic disease were randomly assigned to 6–9 courses of AT q3 wks or double HD with PBSCT. G-CSF-mobilized stem cells were collected before and after the 1st course of HD. HD was repeated after 6 weeks. Pts were stratified by menopausal status and hormone receptor (HR) status. HR positive pts received in addition tamoxifen. The primary objective was to compare complete response rates (CR). Results: Due to inadequate accrual the trial was terminated early in 03/02.Treatment groups (HD 48 pts, AT 45 pts) were well balanced for baseline characteristics (median age 49.7 ys, range 27–60; visceral metastases 87.1%; HR+ 71.0%; premenopausal 40.9%). Intent-to-treat (ITT) objective response rate (RR) was 66.7% for HD vs 64.4% for AT (p=0.82). Per protocol (PP) analysis showed 78.0% RR for HD and 64.4% for AT (p=0.26). There was no significant difference in CR (ITT: HD 12.5% vs AT 11.1%; PP: HD 14.6% vs AT 11.1%). After a median follow-up of 22.5 mths, 75 pts have progressed (HD 36, AT 39) and 66 pts have died (HD 34, AT 32). ITT analysis showed no significant difference in median TTP (HD 11.1 mths, AT 10.6 mths; p=0.39), duration of response (DR) (HD 13.9 mths, AT 14.3 mths; p=0.98), treatment-free interval (HD 9.7 mths, AT 6.6 mths; p=0.24) and OS (HD 26.9 mths, AT 23,4 mths; p=0.60). As expected, HD was associated with significantly more grade 3/4 myelosuppression, nausea/vomiting, infection and stomatitis, but less neuropathy than AT. Conclusions: In contrast to our previous analysis (Schmid, ASCO 2002), there are no significant differences in CR, RR, TTP, DR and OS between HD and AT. HD was associated with more acute adverse effects. No significant financial relationships to disclose.