Metronomic oral Vinorelbine and Temozolomide, after whole brain radiotherapy, for the treatment of breast cancer patients with brain metastasis. A Phase II study

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Background: The incidence of Central Nervous system (CNS) metastases has been reported to be 15–25% in patients with breast cancer. Temozolamide (TMZ) is a new orally administered imidazo-tetrazine with proven activity in Brain metastasis. Vinorelbine The recently introduced oral form of this vinca alkaloid derivative, Vinorelbine, has disclosed new and useful perspectives particularly for elderly patients.

Methods: Patients with breast cancer and newly diagnosed, inoperable, brain metastases (BM) were eligible. We have treated 19 consecutive patients ( mean age: 55.2 + 22.4 years; median age: 57.9 years) affected by brain metastases with WBRT at 3 Gy/d administered over a two-week period (on weeks 1–2), total dose 30Gy, and an induction with TMZ 75mg/m²/d during this period, followed by 4 weeks off-therapy and subsequent original schedule with TMZ administration at 75mg/m² on days 1–21 every and oral Vinorelbine (VNR) 70mg/m² fractionated in days 1, 3 and 5, one week on-one week off, every four weeks up to 12 cycles.

Results: All patients were subjected to the induction therapy. Two grade three, 12 grade II and 10 grade I neutropenia (CTC), 5 grade II anaemia, seven grade I and four grade II thrombocytopenia and nine grade I alopecia were recorded. Fourteen grade I and 7grade III, nausea and vomiting were observed, moreover, liver or renal toxicity were never recorded in our series being the schedule well tolerated in all patients. two CR (10%), and 8 PRs (42%) were recorded whilst a clinical benefit was achieved in other four patients (21%). The Objective Responses rate was 52% (C.I. 42.7–64.9%), whilst the disease control rate was 73% (C.I. 61.7–82.4%). Overall survival was 59% at 1 year.

Conclusions: These preliminary results show that some of the pts who received complete treatment plan could achieve prolonged disease control and survival. The schedule was safe and well tolerated (also in old pts.) and has suggested an encouraging activity in brain metastases from breast cancer.