Therapeutic potential of 5‐[125I]iodo‐2′‐deoxyuridine and methotrexate in the treatment of advanced neoplastic meningitis

Abstract

Purpose: To assess the therapeutic potential of methotrexate (MTX) and 5‐[¹²⁵I]iodo‐2′‐deoxyuridine (¹²⁵IdUrd) administered sequentially in rats bearing advanced (ten‐day‐old) intrathecal (i.t.) TE671 human rhabdomyosarcoma tumours. Materials and methods: Nude rats were injected with TE671 cells through an i.t. placed catheter. Ten days later, the animals were injected i.t. over a 12‐day period with (i) saline daily, (ii) MTX every other day, (iii) ¹²⁵IdUrd every other day, or (iv) MTX and ¹²⁵IdUrd on alternating days. Onset of paralysis was determined as a function of time, and the medians for onset (M), percentage of cells killed (% kill), and log cell kill were calculated. Results: The data show that (i) injection of MTX leads to a moderate delay in the onset of paralysis (M_MTX=29 d versus M_saline=20 d), (ii) administration of ¹²⁵IdUrd is more effective (M_IdUrd=36 d), and (iii) sequential administration of MTX–¹²⁵IdUrd further increases the therapeutic efficacy of ¹²⁵IdUrd (M_MTX–IdUrd=47 d). Conclusions: Intrathecal injection of MTX–¹²⁵IdUrd is efficacious in the therapy of advanced intrathecal tumours.