Phase I dose-escalation study of tezacitabine in combination with 5-fluorouracil in patients with advanced solid tumors.

Abstract

BACKGROUND:

Tezacitabine [(E)-2'-deoxy-2'-(fluoromethylene) cytidine; FMdC] is a novel nucleoside analog with potent antiproliferative and antitumor activity in preclinical studies. A tolerable safety profile and clinical activity have been shown in Phase I and Phase II clinical studies. The purpose of the current open-label, Phase I dose-escalation trial was to evaluate the combination of tezacitabine and 5-fluorouracil (5-FU) in the treatment of patients with advanced solid tumors.

METHODS:

Twenty-four patients with a variety of advanced solid tumors for which there was no curative therapy were enrolled. Bolus infusion tezacitabine was administered on Day 1 of a 14-day cycle at escalating doses of 150-350 mg/m(2), with continuous infusion 5-FU (CI 5-FU) given on Days 1-7 at a fixed dose of 200 mg/m(2) per day. Patients underwent objective tumor evaluation by radiologic methods or clinical examination at baseline and after every fourth treatment cycle.

RESULTS:

The maximum tolerated dose of the combination therapy was determined to be tezacitabine, 200 mg/m(2), with CI 5-FU, 200 mg/m(2) per day. The toxicities were manageable, the most notable being transient severe (National Cancer Institute Common Toxicity Criteria Grade 3 or 4) neutropenia in 23 patients (96%). Eleven (55%) of the 20 assessable patients had partial responses or stabilization of disease. The highest response rate was in patients with primary tumors of esophageal origin.

CONCLUSIONS:

Tezacitabine at a dose of 200 mg/m(2) in combination with CI 5-FU at a dose of 200 mg/m(2) per day was relatively well tolerated and had clinical activity in patients with advanced solid tumors, particularly in patients with esophageal and other gastrointestinal carcinomas.

• Authors: Johanna C Bendell, Joseph P Eder, Jeffrey W Clark, Panagiotis Fidias, Thomas J Lynch, Michael V Seiden, David P Ryan
• Journal: Cancer (Cancer) Vol. 103 Issue 9 Pg. 1925-31 (May 01 2005) ISSN: 0008-543X [Print] United States
• PMID: 15772958 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2005 American Cancer Society.

Chemical References

• Deoxycytidine
• Fluorouracil
• tezacitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Dose-Response Relationship, Drug
• Female
• Fluorouracil (administration & dosage)
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)
• Treatment Outcome