Topotecan Chemotherapy in Patients with Breast Cancer and Brain Metastases: Results of a Pilot Study

Abstract

Background: Symptomatic brain metastases occur in approximately 10–15% of patients suffering from breast cancer and are linked to a clear deterioration of the patient’s condition. Although radiotherapy is recommended as a primary therapy, the optimal management remains controversial. To evaluate the role of topotecan as a primary chemotherapy for brain metastases, we performed a pilot study in patients with metastatic breast cancer. Patients and Methods: 24 patients with newly diagnosed, bidimensionally measurable brain metastases received topotecan, 1.5 mg/m² day, 30-min infusion for 5 days every 3 weeks. A total of 93 courses of therapy were administered (range 1–11, median 3 courses per patient). Prior radiotherapy was excluded. Most of the patients had received prior adjuvant or palliative chemotherapy. Results: 3/24 patients were withdrawn from the study for various reasons, 16/24 patients could be evaluated in terms of their response to therapy; 1 and 5 patients showed complete and partial response to therapy, respectively, and 5 patients had a stable condition. The median time of survival was 6.25 months. Hematologic toxicity was the major side effect, nonhematologic side effects occurred rarely and were tolerable. Conclusions: Our results demonstrate that primary chemotherapy with topotecan is an effective and well-tolerated treatment for patients with breast cancer and CNS metastases. Based on this pilot study, future clinical protocols should be developed including multimodal treatment strategies (i.e. radiotherapy).

Topotecan inhibits cancer cell migration by down-regulation of chemokine CC motif receptor 7 and matrix metalloproteinases

“…Previous clinical reports have highlighted the potential activity of TPT against tumor metastasis [20,21] . In this study, we showed that TPT decreased cancer cell migration via down-regulation of CCR7 and MMPs (MMP-2 and MMP-9).…”

“…TPT has been licensed to be a second line anti-cancer agent for patients who have developed small cell lung cancer (SCLC) [18] and ovarian cancer [19] . In addition to its cytotoxic activity against solid tumors, TPT has shown potential activity against brain metastases from breast cancer [20] and SCLC [21] in numerous clinical reports. However, the molecular mechanism for the anti-metastatic effect of TPT is unknown.…”

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

“…Retrospective case series and case reports have been published, but few chemotherapeutic agents have been prospectively evaluated in the breast cancer population. 4,[8][9][10][11] Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and HER-2. 12 In heavily pretreated patients, lapatinib achieved an investigator-reported objective response rate of 5% to 8% for systemic metastatic disease.…”

Central Nervous System Metastases in HER-2–Overexpressing Metastatic Breast Cancer: A Treatment Challenge

“…In a pilot study by Oberhoff et al [68], 24 patients with newly diagnosed, bidimensionally measurable brain metastases received topotecan at a dose of 1.5 mg/m 2 daily for 5 days on a 3-week schedule. Patients with prior radiotherapy were excluded.…”