Pharmacologic variables associated with the development of neurologic toxicity in patients treated with suramin.
OBJECTIVE
To describe pharmacologic variables correlated with the development of neurologic toxicity in patients treated with suramin.


METHODS
Eighty-one patients were treated with suramin in a phase I study. The rate of drug infusion was continuously adjusted to maintain a preassigned plasma suramin concentration (175, 215, or 275 micrograms/mL) for a fixed duration (2 to 8 weeks).


RESULTS
Eight patients developed grade III/IV neurologic motor impairment (predominantly motor axonal polyneuropathy). All were treated at the 275-micrograms/mL concentration. One patient treated at the 215-micrograms/mL concentration developed grade II motor dysfunction. In addition, seven of nine patients had sensory symptoms. Pharmacologic variables associated with the development of polyneuropathy included total cumulative suramin dose, duration of exposure to plasma concentrations greater than 200 micrograms/mL, and area under the curve (AUC) greater than 200 micrograms/mL.


CONCLUSIONS
Significant neurologic toxicity can result from therapy with suramin, even when dosing is designed to avoid exposure to plasma concentrations greater than 350 micrograms/mL. Future clinical trials of suramin should be designed in such a way as to limit the total cumulative dose to < or = 157 mg/kg given over a period of > or = 8 weeks, limit the period of exposure to plasma suramin concentrations greater than 200 micrograms/mL to < or = 25 days, and limit the AUC greater than 200 micrograms/mL to < or = 48,000 mg.h/AL.
Bitton
R J
RJ
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Figg
W D
WD
Venzon
D J
DJ
Dalakas
M C
MC
Bowden
C
C
Headlee
D
D
Reed
E
E
Myers
C E
CE
Cooper
M R
MR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000139:chemically induced; D015999:Multivariate Analysis; D009422:Nervous System Diseases / Q000139:chemically induced*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy; D013498:Suramin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
D013498:Suramin