Meningeal involvement with metastatic carcinoma of the breast treated with intrathecal methotrexate

Abstract

A patient with signs of meningeal irritation was found to have tumor cells in the cerebrospinal fluid which were metastatic from a small primary carcinoma in the left breast. Treatment with intrathecal methotrexate in dosages up to 1 mg/kg of body weight together with systemic injections of citrovorum factor was tolerated without adverse effect. Her neurologic manifestations cleared and the cerebrospinal fluid changes reverted to normal. The patient died 5 months later of advancing systemic disease with pulmonary involvement. There was no clinical recurrence of any neurologic disorder. Since the blood‐brain barrier impedes the entrance of methotrexate into the central nervous system, the importance of administration by the intrathecal route with a large injection volume is emphasized.

Meningeal carcinomatosis and blindness

“…X-ray therapy, or intrathecal methotrexate (McKelvey, 1968) have been reported to give temporary improvement. A combination of these therapeutic methods in the present case lessened the spinal fluid abnormalities but caused no clinical improvement.…”

Evaluation of osmolality and pH of various concentrations of methotrexate, cytarabine, and thiotepa prepared in normal saline, sterile water for injection, and lactated Ringer's solution for intrathecal administration

“…29 Review of literature A total of 44 reports 3,4,7,8,13-17,30-64 were reviewed. Both IT administration by lumbar puncture 3,4,7,8,[14][15][16][30][31][32][33][34][35]37,38,41,43,65,66 or ommaya reservoir 4,17,36,[38][39][40][41][42][43][44]65,67 was used. Generally, ommaya reservoir or similar access device was used in more recent reports.…”

“…7,36,38,39,[41][42][43][44]65 Some also used patient's own CSF, 30,32,35,40,67 Elliott's B solution Õ (buffered intrathecal electrolyte/dextrose solution), 7,8,33,42 sterile water for injection, 4,[14][15][16]34 and lactated Ringer's solution. 30 The most commonly used volume was about 5 mL, 32,36,39,[41][42][43][44] although even up to about 20 mL has occasionally been used. 3,7,30,33 A few investigators used a mixture of different combination of methotrexate, cytarabine, thiotepa, and hydrocortisone.…”

“…30 The most commonly used volume was about 5 mL, 32,36,39,[41][42][43][44] although even up to about 20 mL has occasionally been used. 3,7,30,33 A few investigators used a mixture of different combination of methotrexate, cytarabine, thiotepa, and hydrocortisone. 16,17,37,[65][66][67] The volume used was similar to the single agent IT chemotherapy, usually at 5 mL.…”

“…3,4,7,8,[14][15][16][17][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Most information on drug concentrations was provided for methotrexate, with an average concentration of about 1-2.5 mg/mL. 3,7,30,[32][33][34]36,39,40,42,44 There was less consistent information on the concentration of cytarabine, ranging from 0.4 to 20 mg/mL. 4,31,35,42 However, concentration higher than 10 mg/mL seemed to be associated with increased toxicity.…”