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Published on: July 25, 2020
A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors
Tracy Murray Stewart1, Apurva A Desai2, Michael L Fitzgerald3
1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, CRB 1, Room 562, Baltimore, MD, 21287, USA. tmurray2@jhmi.edu.
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.
