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Cancer Chemotherapy and Pharmacology

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01-06-2020 | Solid Tumor | Original Article

A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors

Authors: Tracy Murray Stewart, Apurva A. Desai, Michael L. Fitzgerald, Laurence J. Marton, Robert A. Casero Jr.

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2020

Abstract

Purpose

Polyamines are essential for the sustained proliferation and biomass required by tumor cells. Bis-alkylated polyamine analogs are nonfunctional competitors of natural polyamines. Of these, PG-11047, a second-generation unsaturated analog of the polyamine spermine, has demonstrated anticancer activity in cell lines and animal models of multiple cancer types. This report describes the first phase I clinical trial to investigate PG-11047 in patients with advanced refractory metastatic solid tumors.

Methods

Forty-six patients were treated with 60-min intravenous infusions of PG-11047 using a 28-day dosing cycle with treatments on days 1, 8, and 15. Doses ranged from 50 to 750 mg. The treatment period consisted of at least two cycles.

Results

The maximum tolerated dose of PG-11047 administered at this dosing schedule was 610 mg. Dose-limiting toxicities (DLT) were mainly gastrointestinal, including oral/anal mucositis and diarrhea; other DLTs included one case each of angioedema and a grade 3 alanine aminotransferase (ALT) increase. The most common adverse effects were fatigue and anorexia. Stable disease was documented in 30% of patients.

Conclusion

Results of this phase I trial suggest that PG-11047 can be safely administered to patients on the once weekly dosing schedule described. The manageable toxicity profile and high MTD determination provide a safety profile for further clinical studies, including those in combination with current chemotherapeutic agents.

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Title: A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors
Authors: Tracy Murray Stewart
Apurva A. Desai
Michael L. Fitzgerald
Laurence J. Marton
Robert A. Casero Jr.
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Solid Tumor
Cytostatic Therapy
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04082-4

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Abstract

Purpose

Methods

Results

Conclusion

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