A randomised trial of second-line hormone vs single agent chemotherapy in tamoxifen resistant advanced breast cancer

Ar Dixon,J Haybittle,L Jackson,Rw Blamey,S Chan

doi:10.1038/bjc.1992.277

Abstract

Sixty patients with advanced breast cancer unresponsive to tamoxifen have been randomised to receive four course of mitozantrone, 14 mg m-2 (n = 30) intravenously every 3 weeks (9 weeks total) or megesterol acetate, 160 mg bd (n = 30). One in three patients (11 from each group) had substantial disease control for a minimum period of 6 months i.e., lack of progression; seven patients (23%) showed objective response to mitozantrone compared to four (13%) receiving megesterol. Non-progressive disease occurred in all sites, including visceral metastases and receptor negative patients. There were no significant differences between treatment groups in the median time (5 months each) to disease progression response duration or survival (13 months megesterol, 11 months mitozantrone) from commencing second-line therapy. Toxicity was considerably higher in the mitozantrone group. Second-line hormonal therapies can produce similar therapeutic results as those achieved from a short course of a 'short option' single agent cytotoxic in patients who were previously thought hormone insensitive. Provided that the patient does not have life threatening disease a trial of megesterol acetate is worth consideration in that it does not prejudice subsequent response to combination cytotoxic chemotherapy.

Highlights

Stable disease of a minimum duration of 6 months was recorded in seven patients (23%) treated by megesterol acetate and four (13%) treated by mitozantrone; patients (63%) had progressive disease
Pretreatment characteristics known to effect prognosis once metastases appear were evenly distributed amongst the two treatment groups (Table II)
Before dismissing the option of further hormonal therapies, consideration has to be given to the fact that long-term remissions and improved survival are rarely seen in advanced breast cancer treated with cytotoxic chemotherapy (Powels et al, 1980), treatment is aimed at achieving palliative remission of symptoms

Summary

Introduction

Provided that the patient does not have life threatening disease a trial of megesterol acetate is worth consideration in that it does not prejudice subsequent response to combination cytotoxic chemotherapy. We have compared the synthetic progestogen, megesterol acetate (Megace®, Bristol Myers, UK) against a 'soft option' single-agent cytotoxic, mitozantrone (Novantrone®, Lederle, UK) in terms of 1 year progression free rates and survival in a group of patients who had shown no therapeutic response to tamoxifen.

Results

Conclusion