Background: F is a selective estrogen receptor (ER) downregulator antagonist, without agonist properties, effective in postmenopausal ABC ER positive women. So far, a few ongoing trials and no
published data exist on F combined with chemotherapy (CT). Based on pharmacokinetic data, with the approved 250 mg monthly schedule, F takes approximately 3-6 months to reach steady-state levels.
In order to await its efficacy and consequently prevent early failure, association with CT may be a realistic and useful strategy. In this view, we retrospectively assessed the role of combining
oral mCM to F in 2 cohorts (A and B) of heavily pre-treated ABC pts.
Patients and methods: from October 2006 to September 2009, 33 postmenopausal ER ABC pts received F 250 mg via i.m. injection q28 days. In A, 20 pts, after disease progression (PD) -often minimal
bone progression or biomarkers elevation- added mCM (CTX 50 mg p.o. daily, MTX 2.5 mg p.o. twice daily on day 1 and day 4 weekly), continuing F at the same dose. In B, 13 pts started F plus mCM
upfront. Median age prior to treatment start was 61 years (range 44-80). All pts had ER and/or PgR positive disease, one with HER2 amplification. Twenty-one pts (64%) had > 2 metastatic involved
sites and 19 pts (58%) had received ≥4 previous lines for metastatic disease.
Results: Median duration of treatment was 18 weeks (range 7-131). Thirty-two pts were evaluable for response. In A, during F alone, 1 patient (5%) had a partial response (PR), 8 pts (40%) had
stable disease (SD), 11 pts (55%) had PD, and after adding mCM, we observed 11 (55%) SD and 9 (45%) PD. In B, we obtained 7 SD (58%) and 5 PD (42%), 1 patient was not included for early
discontinuation of mCM. Clinical benefit (CB) for A+B was 56% (95% CI 38%-74%). Median time to progression for all pts was 8.3 months (95%CI 6.6-11.7). Mainly due to haematological toxicity, mCM
was stopped in 4 pts (12%) and dose reduction was needed in 2 pts (6%).
Conclusions: Treatment with F plus mCM was effective in ABC and was minimally toxic providing long-term disease control in a high proportion of pts. The prolonged CB, often desired in ABC pts,
supports this regimen as an additional and useful therapeutic tool.