BACKGROUND: Treatment options for patients with recurrent central nervous system (CNS) metastases are limited. Rapid infusion of high-dose intravenous methotrexate (HD IV MTX) penetrates the blood-brain barrier (BBB) and has reported activity in leptomeningeal metastases. METHODS: Medical records were reviewed for all patients treated with HD IV MTX (3.5 g/m2) for CNS parenchymal or leptomeningeal metastases. Radiographic response rate, survival, and toxicity were determined. RESULTS: Thirty-one women and one man with a median age of 52 years (range 33-76) were treated with a total of 141 cycles (median 4, range 1-13). Twenty-nine patients had breast cancer, and one each had cancer of unknown primary (CUP), squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC). An objective radiographic response and stable disease were each observed in nine patients (28%), and 13 (44%) patients progressed. Prior treatment with low-dose MTX for systemic disease did not affect response (P = 0.8). The median overall survival (n = 32) was 19.9 weeks (range 2.9-135.4+) with one patient alive at 135.4 weeks. Myelosuppression and elevated serum hepatic transaminases were the most common acute toxicities (21% and 9% of HD IV MTX cycles, respectively). CONCLUSIONS: HD IV MTX is effective in the treatment of CNS metastases with disease control (response or stable) as a best response in 56% of assessable patients. Further study is warranted.
BACKGROUND: Treatment options for patients with recurrent central nervous system (CNS) metastases are limited. Rapid infusion of high-dose intravenous methotrexate (HD IV MTX) penetrates the blood-brain barrier (BBB) and has reported activity in leptomeningeal metastases. METHODS: Medical records were reviewed for all patients treated with HD IV MTX (3.5 g/m2) for CNS parenchymal or leptomeningeal metastases. Radiographic response rate, survival, and toxicity were determined. RESULTS: Thirty-one women and one man with a median age of 52 years (range 33-76) were treated with a total of 141 cycles (median 4, range 1-13). Twenty-nine patients had breast cancer, and one each had cancer of unknown primary (CUP), squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC). An objective radiographic response and stable disease were each observed in nine patients (28%), and 13 (44%) patients progressed. Prior treatment with low-dose MTX for systemic disease did not affect response (P = 0.8). The median overall survival (n = 32) was 19.9 weeks (range 2.9-135.4+) with one patient alive at 135.4 weeks. Myelosuppression and elevated serum hepatic transaminases were the most common acute toxicities (21% and 9% of HD IV MTX cycles, respectively). CONCLUSIONS:HD IV MTX is effective in the treatment of CNS metastases with disease control (response or stable) as a best response in 56% of assessable patients. Further study is warranted.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: M J Glantz; B F Cole; L Recht; W Akerley; P Mills; S Saris; F Hochberg; P Calabresi; M J Egorin Journal: J Clin Oncol Date: 1998-04 Impact factor: 44.544
Authors: C Christodoulou; D Bafaloukos; P Kosmidis; E Samantas; A Bamias; P Papakostas; A Karabelis; C Bacoyiannis; D V Skarlos Journal: Ann Oncol Date: 2001-02 Impact factor: 32.976
Authors: Kurt A Jaeckle; Tracy Batchelor; Steven J O'Day; Surasak Phuphanich; Pamela New; Glenn Lesser; Allen Cohn; Mark Gilbert; Robert Aiken; Deborah Heros; Lisa Rogers; Eric Wong; Dorcas Fulton; John C Gutheil; Said Baidas; Julia M Kennedy; Warren Mason; Paul Moots; Christy Russell; Lode J Swinnen; Stephen B Howell Journal: J Neurooncol Date: 2002-05 Impact factor: 4.130
Authors: Louis Burt Nabors; Mario Ammirati; Philip J Bierman; Henry Brem; Nicholas Butowski; Marc C Chamberlain; Lisa M DeAngelis; Robert A Fenstermaker; Allan Friedman; Mark R Gilbert; Deneen Hesser; Matthias Holdhoff; Larry Junck; Ronald Lawson; Jay S Loeffler; Moshe H Maor; Paul L Moots; Tara Morrison; Maciej M Mrugala; Herbert B Newton; Jana Portnow; Jeffrey J Raizer; Lawrence Recht; Dennis C Shrieve; Allen K Sills; David Tran; Nam Tran; Frank D Vrionis; Patrick Y Wen; Nicole McMillian; Maria Ho Journal: J Natl Compr Canc Netw Date: 2013-09-01 Impact factor: 11.908
Authors: Marc Chamberlain; Riccardo Soffietti; Jeffrey Raizer; Roberta Rudà; Dieta Brandsma; Willem Boogerd; Sophie Taillibert; Morris D Groves; Emilie Le Rhun; Larry Junck; Martin van den Bent; Patrick Y Wen; Kurt A Jaeckle Journal: Neuro Oncol Date: 2014-05-27 Impact factor: 12.300
Authors: Priya Kumthekar; Sean A Grimm; Michael J Avram; Virginia Kaklamani; Irene Helenowski; Alfred Rademaker; Mary Cianfrocca; William Gradishar; Jyoti Patel; Mary Mulcahy; Katie McCarthy; Jeffrey J Raizer Journal: J Neurooncol Date: 2013-01-25 Impact factor: 4.130