Phase I study of high dose etoposide phosphatase with filgrastim (G-CSF) in the treatment of advanced refractory malignancies.

Abstract

PURPOSE:

To define the maximum tolerated dose of etoposide phosphate when used with G-CSF in the treatment of patients with refractory malignancies.

PATIENTS AND 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.

• Authors: J D Hainsworth, S M Utley, F A Greco
• Journal: Investigational new drugs (Invest New Drugs) Vol. 15 Issue 4 Pg. 325-9 ( 1997) ISSN: 0167-6997 [Print] United States
• PMID: 9547675 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Organophosphorus Compounds
• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• etoposide phosphate
• Etoposide
• Filgrastim

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, therapeutic use)
• Bone Marrow Diseases (chemically induced)
• Drug Resistance, Neoplasm
• Etoposide (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Female
• Filgrastim
• Granulocyte Colony-Stimulating Factor (adverse effects, therapeutic use)
• Humans
• Leukocyte Count
• Male
• Middle Aged
• Neoplasms (drug therapy)
• Organophosphorus Compounds (administration & dosage, adverse effects, therapeutic use)
• Platelet Count
• Recombinant Proteins