Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.
OBJECTIVE
This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms.


METHODS
Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion.


RESULTS
Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL.


CONCLUSIONS
Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.
Thompson
D S
DS
Department of Medicine, Vanderbilt University, Nashville, TN.
Hainsworth
J D
JD
Hande
K R
KR
Holzmer
M C
MC
Greco
F A
FA
D000328:Adult; D001855:Bone Marrow Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D005047:Etoposide