Phase I study of the novel taxane CT-2103 in patients with advanced solid tumors.

Abstract

BACKGROUND:

CT-2103 (Cell Therapeutics, Seattle, Wash.) is a water-soluble macromolecular conjugate of paclitaxel to a polyglutamate backbone, designed to enhance tumor permeability and to improve intratumoral delivery of paclitaxel. Preclinical studies indicate that CT-2103 has substantial antitumor efficacy in xenograft tumor models.

METHODS:

We performed a phase I trial in patients with advanced solid tumors to determine the maximum tolerated doses (MTD) of CT-2103 when administered as short intravenous infusion every 3 weeks.

RESULTS:

Seven patients received a total of 16 cycles (range 1-3) of CT-2103 at doses of 235 and 270 mg/m(2). Two of five patients treated at 235 mg/m(2) and one of two patients treated at 270 mg/m(2) experienced grade 3/4 neutropenia. Four patients experienced a marked increase in PTT within 30 min of the start of infusion. Neuropathy was more severe than expected. Two patients developed grade 3 neuropathy that prompted a 50% dose reduction of CT-2103 and persisted for 8 months in one, and over a year in the other. Three patients experienced grade 1 or 2 neuropathy. Neurotoxicity was cumulative and prevented patients from receiving prolonged administration of CT-2103.

CONCLUSIONS:

The unexpectedly high rate of cumulative toxicity observed in our study needs to be taken into consideration in future trials of CT-2103. Prior taxane use may not be a predictor of severe neurotoxicity.

• Authors: Maria Luisa Veronese, Keith Flaherty, Amy Kramer, Barbara A Konkle, Mark Morgan, James P Stevenson, Peter J O'Dwyer
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 55 Issue 5 Pg. 497-501 (May 2005) ISSN: 0344-5704 [Print] Germany
• PMID: 15711828 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Taxoids
• Polyglutamic Acid
• Paclitaxel
• paclitaxel poliglumex

Topics

• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Nausea (chemically induced)
• Neoplasms (drug therapy)
• Neutropenia (chemically induced)
• Paclitaxel (analogs & derivatives)
• Peripheral Nervous System Diseases (chemically induced)
• Polyglutamic Acid (adverse effects, therapeutic use)
• Taxoids (adverse effects, therapeutic use)
• Thrombocytopenia (chemically induced)
• Treatment Failure