Trial reportPharmacogenetics and genomics2019
An initial genetic analysis of gemcitabine-induced high-grade neutropenia in pancreatic cancer patients in CALGB 80303 (Alliance).
Trial report in Pharmacogenetics and genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.
- A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.Clinical and translational science · 2024Pooled it
- A resource for integrated genomic analysis of the human liver.Scientific reports · 2022Pooled it
- Adjuvant 5-fluorouracil and portal vein infusion chemotherapy followed by gemcitabine for pancreatic cancer.Cancer medicine · 2024Trial
- Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients.British journal of cancer · 2022Trial
- Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance).Angiogenesis · 2022Trial
- Association between ABCB1 genetic polymorphisms with treatment outcomes in patients with metastatic pancreatic cancer.International journal of clinical oncology · 2026Article
- Integrative Mapping of Regulatory Variation in African American Hepatocytes Using Colocalization and MPRA: Toward Precision Drug Response.Research square · 2026Article
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 9 institutions in 4 countries.
Funding
Abstract
objectivesOne of the standard of care regimens for advanced pancreatic cancer is gemcitabine-based chemotherapy. The efficacy of gemcitabine is limited by dose-limiting hematologic toxicities especially neutropenia. Uncovering the variability of these toxicities attributed to germline DNA variation is of great importance. PATIENTS AND
methodsCALGB 80303 was a randomized study in advanced pancreatic cancer patients treated with gemcitabine with or without bevacizumab. The study protocol included genotyping of genes of gemcitabine disposition (CDA, DCTD, SLC29A1, SLC28A1, and SLC29A2), as well as a genome-wide analysis. The clinical phenotype was time to early high-grade neutropenia event accounting for progression or death or other treatment-terminating adverse events as competing for informative events. The inference was carried out on the basis of the association between genotype and cause-specific hazard of a neutropenic event.
resultsThe primary analyses were carried out on the basis of 294 genetically estimated European pancreatic cancer patients. For CDA rs2072671 (A>C), AC and CC patients had a lower risk of neutropenia than AA patients (P=0.01, hazard ratio: 0.61, 95% confidence interval: 0.41-0.89). For SLC28A1 rs3825876 (G>A), AA patients have a higher risk of neutropenia than GA and GG patients (P=0.02, hazard ratio: 1.51, 95% confidence interval: 1.06-2.16). CDA rs2072671 was associated with increased mRNA expression in whole blood in three studies (P=2.7e-14, 6.61e-62, and 9.70e-65). In the genome-wide analysis, variants in TGFB2 were among the top hits (lowest P=1.62e-06) but had no effect in luciferase assays.
conclusionThis is the first genetic analysis of gemcitabine-induced neutropenia using a competing risk model in a prospective randomized clinical study has proposed a potentially novel mechanism of the protective effect of the CDA rs2072671 variant. Further confirmation is needed.
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