ArticleCancer chemotherapy and pharmacology2014
A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors.
Article in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01191775 (A Phase 1 Study of PNT2258 in Patients With Advanced Solid Tumors), which is not on this map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Study of PNT2258 in Patients With Advanced Solid Tumors
Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
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- A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy.International journal of nanomedicine · 2023Review
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- Clinical progress of nanomedicine-based RNA therapies.Bioactive materials · 2022Review
- Emerging Nanotherapeutic Approaches to Overcome Drug Resistance in Cancers with Update on Clinical Trials.Pharmaceutics · 2022Review
- Towards principled design of cancer nanomedicine to accelerate clinical translation.Materials today. Bio · 2022Review
- Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2.Pharmaceutics · 2022Review
- Targeted Downregulation of MYC through G-quadruplex Stabilization by DNAi.Molecules (Basel, Switzerland) · 2021Article
- Noncoding RNA therapeutics - challenges and potential solutions.Nature reviews. Drug discovery · 2021Review
- Therapeutics Targeting the Core Apoptotic Machinery.Cancers · 2021Review
- Nucleic Acid Delivery with Red-Blood-Cell-Based Carriers.International journal of molecular sciences · 2021Review
- Recent Advances in Oligonucleotide Therapeutics in Oncology.International journal of molecular sciences · 2021Review
- Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMaximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were assessed in this phase 1 study of PNT2258, a BCL-2-targeted liposomal formulation of a 24-base DNA oligonucleotide called PNT100.
methodsPatients with malignant solid tumors were assigned sequentially to one of ten dose-escalation cohorts of PNT2258 at 1, 2, 4, 8, 16, 32, 64, 85, 113, and 150 mg/m(2) administered intravenously on days 1 through 5 of each 21-day cycle. Pharmacokinetics were determined on days 1 and 5 of the first cycle. Lymphocyte and platelets concentrations were measured for evidence of BCL2-targeted effect. CT scans were used to identify radiologic evidence of anti-tumor effect.
resultsTwenty-two subjects received PNT2258, and the maximum tolerated dose for PNT2258 was not reached. Doses at or above 32 mg/m(2) resulted in exposure to PNT2258 above the exposure level required for anti-tumor activity in preclinical xenograft testing of 22,377 ng h/ml (PK analysis 2012). Fatigue was the most commonly reported adverse event. Dose-limiting toxicity, manifesting as a transient increase in aspartate aminotransferase, occurred at 150 mg/m(2), the highest dose tested. Four subjects, two each with diagnosis of non-small-cell lung cancer and sarcoma, treated at doses of 64 mg/m(2) or higher, remained on study for 5-8 cycles.
conclusionsPNT2258 was safe and well tolerated at the doses tested up to 150 mg/m(2). Exposure to PNT2258 resulted in clinically manageable decreases in lymphocyte and platelet concentrations.
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Registered trials
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