UGT1A1*28

P2, N=78, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jun 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=60, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

To date, the clinical benefit and utility of implementing a DPYD/UGT1A1 pharmacogenetic-informed therapy with fluoropyrimidines and/or irinotecan have not been prospectively investigated...Clinical benefit did not appear to be affected. ClinicalTrials.gov Identifier: NCT03093818.

PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings.

P2, N=50, Active, not recruiting, Fudan University | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Jul 2025

Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data.

P1/2, N=64, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

Methods Pts with cT2-4N0M0 MIBC with pure/predominant urothelial carcinoma histology, who were ineligible for or refused cisplatin-based chemotherapy, received 4 cycles of SG 10 mg/kg (days 1,8 q3w) followed by RC. Conclusions The observed ypT0N0-x responses after neoadjuvant SG demonstrate promising activity in MIBC, unveiling a potential to avoid RC. Reduced dose of SG was feasible, and the data support the ongoing SURE-01 study in MIBC.

P2, N=60, Not yet recruiting, National Cancer Institute (NCI)

Hence, screening for UGT1A1 polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on UGT1A1*28 and UGT1A1*6 variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of UGT1A1 genotype testing.

One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.

The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.