Journal of Clinical Oncology, Vol 15, 3141-3148, Copyright © 1997 by American Society of Clinical Oncology
Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. Australian-New Zealand Breast Cancer Trials Group
MJ Byrne, V Gebski, J Forbes, MH Tattersall, RJ Simes, AS Coates, J Dewar, M Lunn, C Flower, PG Gill and J Stewart
Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. mjbyrne@cyllene.uwa.edu.au
PURPOSE: To determine whether a strategy of adding medroxyprogesterone
acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for
TAM among women with advanced breast cancer and disease progressing on TAM.
To assess the patterns or response and subsequent progression in sites and
tissues according to prior involvement and treatment. PATIENTS AND METHODS:
Two-hundred-fifteen postmenopausal women with advanced breast cancer
progressing on TAM after receiving TAM for at least six months were
randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop
TAM and to substitute MPA. RESULTS: There were no significant differences
between the groups with respect to complete plus partial response rates:
TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA
4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4
months. In a multivariate model, prognostic factors significant for a
shorter time to disease progression were worse for performance status,
involvement of more than one tissue, prior radiotherapy, and shorter time
from recurrence after primary therapy to randomization. Adjusting for these
factors, treatment with TAM + MPA was associated with a higher relative
risk for disease progression, with a hazards ratio of 1.31, but this was
not significant (95% confidence interval, 0.98 to 1.74; P = .067). However,
in an exploratory analysis, the time to disease progression, among patients
with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA
versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95%
confidence interval, 1.12 to 3.32; P = .02). There was a significant
interaction, P = .04, between PR status and treatment, indicating an
advantage to treatment substitution for those who have PR+ tumors. Tumor
response occurred in 14% of assessed metastatic sites. Subsequent
progression occurred in a new tissue alone in 13% of patients, in both new
and previously involved (old) tissues in 76%, and in old tissues only in
11%. In 23% of patients, progression occurred only at a new site, in 50% at
both old and new sites, and in 27% only at old sites. No significant
differences in the patterns of response or progression were seen in the
different treatment groups. CONCLUSION: Among women with breast cancer
whose disease is progressing after at least six months of treatment with
TAM, there is no advantage to maintaining TAM when MPA is to be given. An
overall effect of treatment on the pattern of failure at old sites or at
new sites or tissues cannot be discerned.
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