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Cancer, Stress, Anesthesia, and Immune Response · Journal article
Frontiers in Pain Research · August 17, 2026
Early or partial results. Treat as a signal, not a conclusion.
This single-center prospective study of 49 cancer patients receiving transdermal fentanyl found no robust associations between tested pharmacogenetic variants (TPMT, UGT2B7, CYP3A4/5, ABCB1) and fentanyl pharmacokinetics, analgesic response, or adverse events after correction for multiple testing. Although unadjusted associations were observed, the authors explicitly conclude that the findings do not support clinical implementation of pharmacogenetic-guided TDF therapy at this time.
Single-center, prospective biological study. Adults with solid or hematological malignancies and chronic cancer pain treated with stable-dose 72-hour TDF; median age 65 years; 98% stage IV disease.. Intervention: Transdermal fentanyl (TDF) 72-hour patches at stable dose; pharmacogenetic panel including TPMT, UGT2B7, CYP3A4/5, and ABCB1. Compared with: Comparison between genetic responders and non-responders; no active control arm. n = 49. Single center (location not specified).
49 patients enrolled (median age 65 years; 98% stage IV disease); 38 (77.5%) were analgesic responders No significant differences in AUC, Cmax, or tmax between responders and non-responders TPMT and UGT2B7 variants showed unadjusted associations but none remained statistically significant after correction for multiple testing
No significant associations observed for CYP3A4/5 or ABCB1 variants, nor between genetic variants and adverse events
Clinicians should not implement pharmacogenetic testing to guide transdermal fentanyl dosing in cancer patients based on this evidence. The negative findings after multiple-testing correction suggest that common variants in major fentanyl-metabolizing genes do not meaningfully predict analgesic response or tolerability in this population.
Single-center exploratory cohort with negative primary findings after multiple-testing correction; provides hypothesis-generating signals but insufficient evidence to guide clinical pharmacogenetic testing for fentanyl.
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Clinicians should not implement pharmacogenetic testing to guide transdermal fentanyl dosing in cancer patients based on this evidence. The negative findings after multiple-testing correction suggest that common variants in major fentanyl-metabolizing genes do not meaningfully predict analgesic response or tolerability in this population.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background/objectives Transdermal fentanyl (TDF) is widely used for moderate-to-severe cancer pain, yet substantial variability in fentanyl exposure, analgesic response, and tolerability remains incompletely explained by clinical factors. We evaluated whether pharmacogenetic variability is associated with pharmacokinetic parameters and clinical outcomes in cancer patients receiving TDF. Methods In this prospective, single-center study, adults with solid or hematological malignancies and chronic cancer pain treated with stable-dose 72 h TDF were enrolled. Blood samples were collected for pharmacokinetic and pharmacogenetic analyses. Serum fentanyl concentrations were quantified using validated gas chromatography–mass spectrometry, and AUC, C max, and t max were calculated using non-compartmental analysis. Genotyping was performed using a predefined pharmacogenetic panel. Analgesic response was defined as a ≥2-point reduction in Numeric Rating Scale score or score = 0 at 72 h. Statistical analyses included correction for multiple testing. Results 49 patients were included (median age 65 years; 98% stage IV disease); 38 (77.5%) were responders. No significant differences in AUC, C max, or t max were observed between responders and non-responders. TPMT and UGT2B7 variants showed unadjusted associations with clinical response and pharmacokinetic parameters, respectively; however, none remained statistically significant after correction for multiple testing. No significant associations were observed for CYP3A4/5 or ABCB1 variants, nor between genetic variants and adverse events. Pain reduction correlated with improved functional outcomes. Conclusions In this exploratory cohort, pharmacogenetic variability was not robustly associated with TDF pharmacokinetics, analgesic response, or tolerability after correction for multiple testing. These findings do not support the current clinical implementation of pharmacogenetic-guided TDF therapy, but provide hypothesis-generating signals for future studies.
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