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.
Original language | English (US) |
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Pages (from-to) | 1089-1096 |
Number of pages | 8 |
Journal | Cancer Chemotherapy and Pharmacology |
Volume | 85 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1 2020 |
Keywords
- Bis-alkyl polyamine analog
- Cancer
- Chemotherapy
- Clinical trial
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)