A phase I study of the antimetabolite (E)-2'-fluoromethylene-2'-deoxycytidine (MDL 101,731) administered as a twice-weekly infusion.

Abstract

PURPOSE:

(E)-2'-fluoromethylene-2'-deoxycytidine is a novel antimetabolite. Preclinical tests have shown antiproliferative activity in various human tumor xenograft models and have also indicated that efficacy is greatest with frequent dosing schedules. We conducted a phase I trial of MDL 101,731 infusion in humans with advanced cancer to determine the maximum tolerated dose and the dose-limiting toxicities of this drug when administered on a twice-weekly schedule.

PATIENTS AND METHODS:

The drug was administered on a twice-weekly schedule for 3 weeks, followed by a 2-week rest. The initial dose was 16 mg/m2. This was reduced to 12 mg/m2 if persistent neutropenia occurred. All toxicity in the first six patients resolved by the end of the first rest week. The schedule was changed to 3 weeks of therapy followed by 1 rest week for the subsequent four patients.

RESULTS:

Dose escalation beyond 16 mg/m2 was not feasible because of dose-limiting toxicities, principally hematologic. No irreversible or life-threatening toxicity was seen. Grade 2 noninfectious fever, mucositis, and anorexia were also seen. In patients with stable disease, there was a heavily pretreated patient with rectal cancer in whom a 38% reduction in indicator lesions of 7 months' duration occurred.

DISCUSSION:

(E)-2'-fluoromethylene-2'-deoxycytidine is a novel antimetabolite with evidence of anticancer activity in heavily pretreated patients. The maximum tolerated dose when the agent is given twice weekly is 16 mg/m2.

• Authors: B Burtness, M Belker, M Stoltz, K M Peccerillo, L A Lamb, S E Chmael, A McKeon, M B Clark, J Winship, J C Marsh, G Pizzorno, V T DeVita Jr
• Journal: Cancer journal (Sudbury, Mass.) (Cancer J) 2000 Sep-Oct Vol. 6 Issue 5 Pg. 309-15 ISSN: 1528-9117 [Print] United States
• PMID: 11079170 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Deoxycytidine
• tezacitabine

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use, toxicity)
• Deoxycytidine (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use, toxicity)
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)
• Time Factors
• Treatment Outcome