Protracted low dose of oral vinorelbine and temozolomide with whole-brain radiotherapy in the treatment for breast cancer patients with brain metastases.

Abstract Purpose The management of brain metastases (BM) from breast cancer (BC) needs to be improved, and new therapeutic strategies are urgently requested. In this view, we have evaluated the efficacy, tolerability, and safety of concurrent low protracted dose of temozolomide (TMZ), metronomic oral vinorelbine (VNB), and radiotherapy in BC women with previously untreated BM. Methods Thirty-six patients with newly diagnosed BM were treated with TMZ orally administered at a dose of 75 mg/m2 during whole-brain radiotherapy, followed by 4 weeks off-therapy and a subsequent administration of oral 70 mg/m2 VNB fractionated in days 1, 3, and 5, weekly for three consecutive weeks plus TMZ at 75 mg/m2 on days 1–21, all every 4 weeks for up to 12 additional cycles. The primary end point was the evaluation of the objective response rate (ORR). Results Three complete responses and 16 partial responses have been achieved with an ORR of 52 % (95 % CI 38–67 %) that exceeded the target activity per study design. The median progression-free survival and overall survival were 8 and 11 months, respectively. The schedule appeared to be well tolerated, and side effects were generally mild. The functional assessment of cancer therapybreast (FACT-B) analysis showed a significant positive change during the study. Conclusions In conclusion, the treatment was safe and a significant number of objective responses were observed with a significant improvement in quality of life demonstrated by FACT-B. On the basis of the present results, a large randomized trial is warranted in BC patients with previously untreated BM.