Phase I study of folate conjugate EC145 (Vintafolide) in patients with refractory solid tumors.

Abstract

PURPOSE:

EC145 (vintafolide), a conjugate of folic acid and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), is a ligand for the folate receptor (FR), with activity against FR-positive tumor xenografts in vivo. This phase I study determined the maximum-tolerated dose (MTD) of EC145 administered as a bolus intravenous injection or 1-hour infusion in patients with refractory solid tumors.

PATIENTS AND METHODS:

EC145 was administered as a bolus injection or 1-hour infusion on days 1, 3, and 5 and days 15, 17, and 19 of each 28-day cycle with dose escalation in cohorts of three to six patients until the MTD was identified. Plasma pharmacokinetics were determined on days 1 and 3 of the first cycle.

RESULTS:

The MTD of EC145 was 2.5 mg when administered as either a bolus injection or 1-hour infusion. Constipation was the dose-limiting toxicity with both routes. Constipation, nausea, fatigue, and vomiting were the most commonly reported adverse events. One partial response to therapy was observed in a patient with metastatic ovarian cancer.

CONCLUSION:

EC145 administered by bolus injection or as a 1-hour infusion at a dose of 2.5 mg on days 1, 3, and 5 and days 15, 17, and 19 of a 28-day cycle has an acceptable safety profile in patients with advanced cancer. On the basis of these findings, phase II studies of EC145 have been initiated in patients with advanced epithelial ovarian cancer and non-small-cell lung cancer.

• Authors: Patricia M Lorusso, Martin J Edelman, Susan L Bever, Karen M Forman, Maryjo Pilat, Mary F Quinn, Jing Li, Elisabeth I Heath, Lisa M Malburg, Patrick J Klein, Christopher P Leamon, Richard A Messmann, Edward A Sausville
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 32 Pg. 4011-6 (Nov 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 23032618 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• EC145
• Vinca Alkaloids
• Folic Acid

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, blood, pharmacokinetics)
• Constipation (chemically induced)
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Fatigue (chemically induced)
• Female
• Folic Acid (administration & dosage, adverse effects, analogs & derivatives, blood, pharmacokinetics)
• Humans
• Infusions, Intravenous
• Injections, Intravenous
• Male
• Maximum Tolerated Dose
• Middle Aged
• Nausea (chemically induced)
• Neoplasms (blood, drug therapy)
• Severity of Illness Index
• Vinca Alkaloids (administration & dosage, adverse effects, blood, pharmacokinetics)
• Vomiting (chemically induced)