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Impact of the Duration of Diabetes Mellitus on the Outcome of Metastatic Pancreatic Cancer Treated with Gemcitabine: A Retrospective Study.

ABSTRACT: Objective To assess the impact of the duration of diabetes mellitus (DM) on the outcomes of pancreatic cancer patients undergoing chemotherapy. Methods We reviewed the medical records of patients with metastatic pancreatic cancer who received gemcitabine monotherapy as the standard therapy before the introduction of combination regimens. The treatment outcomes of gemcitabine were compared among three groups classified according to the duration of DM: no DM, short DM (<4 years), and long DM (?4 years). Results Among 350 patients, 218, 87, and 45 patients were classified into the no DM, short DM, and long DM groups, respectively. In comparison to the no DM group, the univariate hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were 1.44 [95% confidence interval (CI), 1.02-2.02; p=0.027] and 1.33 (95% CI, 0.93-1.89; p=0.081), respectively, in the long DM group, and 1.12 (95% CI, 0.85-1.46; p=0.426) and 1.06 (95% CI, 0.81-1.40; p=0.678), respectively, in the short DM group; the multivariate-adjusted HRs were 1.33 (95% CI, 0.94-1.89; p=0.103) and 1.37 (95% CI, 0.95-1.98; p=0.095) in the long DM group and 1.12 (95% CI, 0.85-1.47; p=0.410) and 1.10 (95% CI, 0.82-1.46; p=0.533) in the short DM group. The survival outcomes of the long DM group tended to remain poorer in analyses using different cutoffs of DM duration as, well as in hospital-specific analyses. Conclusion Long-standing DM may be associated with shorter PFS and OS in patients with metastatic pancreatic cancer.

SUBMITTER: Iizumi S

PROVIDER: S-EPMC6761348 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Impact of the Duration of Diabetes Mellitus on the Outcome of Metastatic Pancreatic Cancer Treated with Gemcitabine: A Retrospective Study.

Iizumi Sakura S Kuchiba Aya A Okusaka Takuji T Ikeda Masafumi M Sakamoto Yasunari Y Kondo Shunsuke S Morizane Chigusa C Ueno Hideki H Osame Keiichiro K Mitsunaga Shuichi S Ohno Izumi I Imaoka Hiroshi H Hashimoto Yusuke Y Takahashi Hideaki H Sasaki Mitsuhito M Ohashi Ken K

Internal medicine (Tokyo, Japan) 20190607 17

Objective To assess the impact of the duration of diabetes mellitus (DM) on the outcomes of pancreatic cancer patients undergoing chemotherapy. Methods We reviewed the medical records of patients with metastatic pancreatic cancer who received gemcitabine monotherapy as the standard therapy before the introduction of combination regimens. The treatment outcomes of gemcitabine were compared among three groups classified according to the duration of DM: no DM, short DM (<4 years), and long DM (≥4 y ...[more]

PMID: 31178491

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Project description:IntroductionNeonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth.Material and methodsThis Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019-2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models.ResultsIn the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74-0.96), vs MIT (0.74 [0.64-0.87]), and vs IT (0.47 [0.40-0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99-1.30]) and with lower risk vs IT (0.63 [0.53-0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories.ConclusionsThe risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors.

Project description:PurposeBecause cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships.Experimental designOne hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine.ResultsFive patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity <1.3 U/mg), and only one among them experienced early severe hematological toxicity. There was no statistically significant difference in CDA activity between patients experiencing hematological severe toxicities (28.44%) and patients who tolerated the treatment (71.56%). CDA genetic analysis failed in evidencing an impact in terms of toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter-individual variability has been observed in patients.ConclusionThis study, which included only 4.6% of CDA-deficient patients, failed in identifying CDA status as a predictive marker of toxicities with gemcitabine. A lack of statistical power because of smoothing effect of CDA variability as compared with real life conditions could explain this absence of impact.Trial registrationClinicalTrials.gov NCT01416662.

Dataset Information

Impact of the Duration of Diabetes Mellitus on the Outcome of Metastatic Pancreatic Cancer Treated with Gemcitabine: A Retrospective Study.

Publications

Impact of the Duration of Diabetes Mellitus on the Outcome of Metastatic Pancreatic Cancer Treated with Gemcitabine: A Retrospective Study.

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