HER2 Support Group Forums - View Single Post - Intrathecal Herceptin/Topotecan for Leptomeningeal Disease

Lani · 05-19-2012, 04:49 PM

Hot off the "press"

Reading the abstracts for the upcoming ASCO annual meeting I found this:

2015 Poster Discussion Session (Board #3), Fri, 1:00 PM-5:00 PM and 4:30 PM-5:30 PM
Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) asso- ciated with 􏰑responsive􏰑 malignancies.
Kurt A. Jaeckle, S. Keith Anderson, Anna Willson, Gerardo Colon-Otero, Tejal Amar Patel, Edith A. Perez; Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Memorial Healthcare Systems, Hollywood, FL
Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent 􏰂 CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had 􏰂 CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13􏰂, 30􏰂, 33􏰂, and 180􏰂 wks. 4 pts (24%) lived 􏰁 95 wks. Of 11 w/ baseline 􏰂 CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear 􏰃 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.

05-19-2012, 04:49 PM	#12
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease Hot off the "press" Reading the abstracts for the upcoming ASCO annual meeting I found this: 2015 Poster Discussion Session (Board #3), Fri, 1:00 PM-5:00 PM and 4:30 PM-5:30 PM Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) asso- ciated with 􏰑responsive􏰑 malignancies. Kurt A. Jaeckle, S. Keith Anderson, Anna Willson, Gerardo Colon-Otero, Tejal Amar Patel, Edith A. Perez; Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Memorial Healthcare Systems, Hollywood, FL Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent 􏰂 CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had 􏰂 CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13􏰂, 30􏰂, 33􏰂, and 180􏰂 wks. 4 pts (24%) lived 􏰁 95 wks. Of 11 w/ baseline 􏰂 CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear 􏰃 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.