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


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.
Kassis
Amin I
AI
Harvard Medical School, Armenise Building, D2-137, 200 Longwood Avenue, Boston, MA 02115-5729, USA. amin_kassis@hms.harvard.edu
Kirichian
Agop M
AM
Wang
Ketai
K
Semnani
Elham Safaie
ES
Adelstein
S James
SJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004357:Drug Synergism; D007065:Idoxuridine / Q000008:administration & dosage*; D007278:Injections, Spinal; D008577:Meningeal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D008581:Meningitis / Q000209:etiology / Q000517:prevention & control*; D008727:Methotrexate / Q000008:administration & dosage*; D010166:Palliative Care / Q000379:methods; D010243:Paralysis / Q000209:etiology / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D051381:Rats; D012208:Rhabdomyosarcoma / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D012720:Severity of Illness Index; D013125:Spinal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000532:radiotherapy*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D019275:Radiopharmaceuticals; D007065:Idoxuridine; D008727:Methotrexate