Therapeutic potential of 5-[125I]iodo-2'-deoxyuridine and methotrexate in the treatment of advanced neoplastic meningitis.

Purpose: To assess the therapeutic potential of methotrexate (MTX) and 5-[1251]liodo-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 Msaline = 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-(125)IdUrd is efficacious in the therapy of advanced intrathecal tumours.