Phase I study of high dose etoposide phosphatase with filgrastim (G-CSF) in the treatment of advanced refractory malignancies.
OBJECTIVE
To define the maximum tolerated dose of etoposide phosphate when used with G-CSF in the treatment of patients with refractory malignancies.


METHODS
Eleven patients with advanced cancer refractory to standard therapy were treated with etoposide phosphate given over 1-2 hours on three consecutive days. The first cohort of patients received a total dose of 1596 mg/m2 (equivalent to etoposide 1400 mg/m2); doses were escalated in subsequent patient cohorts. G-CSF 5 micrograms/kg was administered subcutaneously from day 4 until the total leukocyte count rose to > 10,000/microL. Two courses were given at 28 day intervals.


RESULTS
Toxicity produced by high dose etoposide phosphate included myelosuppression and mucositis. Three of five patients treated at the 2280 mg/m2 dose level (equivalent to etoposide 2000 mg/m2) had dose limiting toxicities (grade 4 leukopenia for 7 days, 2 patients; grade 4 mucositis + leukopenia, 1 patient). In addition, median days with severe thrombocytopenia (< 50,000/microL) rose to six days at this dose. Other toxicity was uncommon.


CONCLUSIONS
In pretreated patients, the maximum tolerated dose of etoposide phosphate with G-CSF is 1938 mg/m2 (equivalent to etoposide 1700 mg/m2). Dose-limiting toxicities were myelosuppression and mucositis, as with high dose etoposide. Etoposide phosphate can be substituted for etoposide in high dose regimens; due to its greater solubility, administration can be more rapid, requires less fluid volume, and is not associated with acidosis.
Hainsworth
J D
JD
Sarah Cannon Cancer Center, Centennial Medical Center, Nashville, Tennessee, USA.
Utley
S M
SM
Greco
F A
FA
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010976:Platelet Count; D011994:Recombinant Proteins
D000972:Antineoplastic Agents, Phytogenic; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C061400:etoposide phosphate; D005047:Etoposide; D000069585:Filgrastim