Maintenance treatment with medroxyprogesterone acetate in patients with advanced breast cancer responding to chemotherapy: results of a randomized trial

Abstract

The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3-weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent-to-treat analysis (p = 0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p = 0.012). Seven patients were removed from MPA due to side effects. The changes in patient-rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p = 0.39). In conclusion, in patients with advanced breast cancer achieving remission or non-progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.

Maintenance Hormone Therapy with Letrozole after First-Line Chemotherapy for Advanced Breast Cancer

“…However, without a quantification of these effects, this clinical practice is hardly defensible as evidence based. The only prospective study available so far was conducted with medroxyprogesterone acetate in a mixed population of ER-positive and ER-negative patients [5]; two other studies have suggested benefit from maintenance hormone therapy after conventional [11] and high-dose chemotherapy [12], respectively, but their retrospective nature does not allow firm conclusions.…”

“…This strategy, however, has not been adequately explored so far. Only one prospective study has been published [5], where medroxyprogesterone acetate was administered as maintenance therapy after first-line chemotherapy in a group of patients, which included premenopausal (48%) and estrogen-receptor (ER)-negative (39%) women. Despite these limitations, the study showed a significant, albeit modest improvement of TTP, from 3.7 months in the control group to 4.9 months in the medroxyprogesterone acetate group.…”

Progesterone enhances cytokine-stimulated nitric oxide synthase II expression and cell death in human breast cancer cells

“…Furthermore, in agreement with the results presented here, the role of Pg in the induction of apoptosis via induction of NOSII to increase NO levels was shown in ovarian cancer cells, 30 indicating a general function of Pg in this mechanism. In fact, several randomised studies and clinical trials have shown that treatment with progestogens led to significant though modest improvement of the relapse-free survival, 42,43 and that inclusion of progestogens in hormone replacement therapy reduces the risk of recurrence, which is associated with an increase in the apoptosis/proliferation ratio within the tumour. 44 The balance between cell death and cell proliferation determines tumour growth rate and even a small alteration in these parameters can be important for the expansion or regression of malignant tumours.…”

Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy

“…Another small study in metastatic breast cancer patients receiving conventional epirubicin therapy suggested a possible survival benefit from MET. 15 The only randomized trial assessing the role of MET in MBC patients has shown a modest improvement in PFS of MBC patients responding to six cycles of epirubicin and ifosfamide; 16 the administration of medroxyprogesterone acetate to 46 patients resulted in a PFS gain of 1.2 months Bone Marrow Transplantation compared to 44 patients in the control group. The small sample size, the inclusion of receptor-negative patients, and the use of an older generation endocrine compound limit the interpretation of this trial.…”