Intrathecal administration of interleukin-2 for meningeal carcinomatosis due to malignant melanoma: sequential evaluation of intracranial pressure, cerebrospinal fluid cytology, and cytokine induction.
A patient with interleukin (IL)-2 responsive metastatic melanoma developed meningeal carcinomatosis. Treatment was attempted with intrathecal (i.t.) IL-2 (5 weekly doses of 3-6 x 10(6) IU) without glucocorticosteroids. Marked increases in cerebrospinal fluid (CSF) pressure occurred 5-10 h following each IL-2 dose, resulting in reversible abnormalities of neurologic function. IL-2 clearance from the CSF ranged from 21 to 85 ml/h, with an apparent first order rate constant of 0.08-0.23 hr-1. These values were consistent with clearance by bulk flow mechanisms. Clearance also correlated directly with peak CSF pressure. Progressive increases in CSF tumor necrosis factor (TNF)-alpha and IL-6 levels, but not Il-1 alpha, were also noted over successive treatment cycles. Increasing neutrophilia (peaking at 12 h postdose) and a delayed lymphocytosis and monocytosis (at 20-30 h) were observed with each successive i.t. IL-2 dose. Activated lymphocytes were not observed in the CSF, however, suggesting that an exogenous source of activated lymphokine-activated killer (LAK) cells may be helpful in obtaining effective antitumor responses.
Samlowski
W E
WE
University of Utah/VAMC Cancer Immunotherapy Program, Salt Lake City.
Park
K J
KJ
Galinsky
R E
RE
Ward
J H
JH
Schumann
G B
GB
D000328:Adult; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary*; D002555:Cerebrospinal Fluid / Q000166:cytology; D015170:Cerebrospinal Fluid Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D007427:Intracranial Pressure / Q000187:drug effects; D015979:Killer Cells, Lymphokine-Activated; D008545:Melanoma / Q000188:drug therapy*; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000556:secondary*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha