Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases. (3rd September 2020)

• Record Type: Journal Article
• Authors: Jaeckle, Kurt A.; Dixon, Jesse G.; Anderson, Stephen Keith; Moreno‐Aspitia, Alvaro; Colon‐Otero, Gerardo; Hebenstreit, Kathy; Patel, Tejal A.; Reddy, Samarth L.; Perez, Edith A.
• Is Part Of: Cancer medicine. Volume 9:Number 21(2020)
• Page Start: 7935
• Page End: 7942
• Publication Date: 2020-09-03
• Subjects: breast cancer -- leptomeningeal metastasis -- neoplastic meningitis -- topotecan; 616.994005
• DOI: 10.1002/cam4.3422
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: There are few treatment options for patients with leptomeningeal metastases (LM). Methods: We report a case series of patients with breast cancer and LM treated with intra‐CSF topotecan (TOPO). Outcome was assessed by clinical exam and MRI at baseline, at end of induction (4‐5 weeks), then every 3 months; CSF cytology was determined at baseline and with each treatment. Results: Thirty‐one women [median age, 58 (37‐81); median KPS 60 (40‐100)] received treatment. At baseline, 68% had positive CSF cytology, and 90%, leptomeningeal enhancement on MRI. 84% of patients also received focal RT (not during TOPO) and 77% received concomitant systemic hormonal or chemotherapy. Median number of TOPO treatments was 14.5 (range, 3‐71); median duration of treatment, 11 weeks (1‐176); and median OS, 6.9 months (range, 0.9‐48.8). Patients remaining progression‐free during 4‐6 weeks of induction (81%) had a median OS of 11.5 months (range, 1.8‐48.8). Overall neurologic PFS at 6, 12, and 24 months was 39%, 26%, and 6%, respectively. Clearing of CSF malignant cells for >3 consecutive samples occurred in 10/21 (48%) patients with positive CSF cytology at baseline, remaining clear for a median duration of 15.9 months (range, 1.4‐34.5). Grade 3 adverse events included headache or vomiting (3pts), T2 hyperintensity surrounding the ventricular catheter (2 pts), and meningitis (2 pts). Conclusions: Intra‐CSF TOPO, with focal RT as needed for symptomatic areas of enhancement produced durable clearing of CSF malignant cells in 48% of patients positive at baseline, with promising median PFS and OS. Abstract : In this case series, intra‐CSF topotecan treatment of women with leptomeningeal metastases and breast cancer was associated with durable CSF clearing of malignant cells in 48% of patients, median OS of 6.9 months, and 11.5 months in those completing 4‐6 weeks induction. Thirty‐two percentage of patients remained free of neurologic progression at 12 months. A method for treatment of patients with VP shunts and programmable valves is also described.