Diabetes mellitus tipo 2 y toxicidad por quimioterapia en adultos mayores con cáncer prostático

Fernando M. Runzer-Colmenares, Diego Chambergo-Michilot, Geraldine A. Espinoza-Gutierrez, Rodrigo Corcuera-Ciudad, Ana F. Patiño-Villena, Rosmery Paima-Olivari, Maria G. Luján Peche, Manuel Cabrera-Lopez, José F. Parodi

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Introducción: Siendo el cáncer prostático una neoplasia prevalente, el envejecimiento es un factor para la toxicidad quimioterapéutica, adicionalmente puede incrementarse por enfermedades crónicas, destacando la diabetes. A pesar de estos conocimientos, no hay estudios que evalúen la asociación entre la diabetes y el riesgo de toxicidad quimioterapéutica en estos pacientes. 

Objetivo: Determinar la asociación entre diabetes mellitus tipo 2 y riesgo de toxicidad por quimioterapia en adultos mayores con cáncer prostático del Servicio de Geriatría del Centro Médico Naval del Perú.

Material y métodos: Estudio analítico de cohorte retrospectiva, análisis secundario de una base de datos. Se evaluaron los efectos adversos de quimioterapia y factores asociados de 161 marinos retirados con cáncer prostático entre 2013 y 2015. Se construyó un modelo de regresión de Cox sobre la toxicidad ajustado por el antecedente de diabetes, edad, antecedentes patológicos, antecedentes de consumo de tabaco, circunferencia de pantorrilla, actividad física, dependencia para ABVD, caídas, polifarmacia, fragilidad y vulnerabilidad.

Resultados: El 23.6% presentó diabetes. La prevalencia de fragilidad fue del 39.7% y de vulnerabilidad, del 24.2% (G8) y 26.71% (VES-13). Los efectos adversos frecuentes fueron gastrointestinales (13.04%) y hematológicos (8.07%). Mediante el modelo de regresión ajustado, el antecedente de diabetes mellitus tipo 2, 3 o más antecedentes patológicos, antecedente de consumo de tabaco, circunferencia de pantorrilla, actividad física, dependencia de ABVD, caídas, polifarmacia, vulnerabilidad y fragilidad presentaron asociación significativa.

Conclusiones: El antecedente de diabetes mellitus tipo 2 es un factor predictivo para el riesgo de toxicidad por quimioterapia en adultos mayores con cáncer prostático.

Palabras clave: diabetes mellitus, toxicidad, quimioterapia, adultos mayores, cáncer, próstata, cohorte






Introduction: Prostate cancer being a frequent neoplasia, aging is a factor for antineoplastic therapy toxicity, it can also be increased by chronic diseases, highlighting diabetes. Despite this knowledge, there are no studies that evaluate the association between diabetes and the risk of antineoplastic therapy toxicity in these patients.

Objective: To determine the association between type 2 diabetes mellitus and the risk of antineoplastic therapy toxicity in aged diagnosed with prostate cancer from Centro Medico Naval del Peru Geriatrics Service.

Material and methods: Retrospective cohort, analytical study, secondary analysis of a database. The adverse effects of antineoplastic therapy and associated factors of 161 retired sailors with prostate cancer between 2013 and 2015 were evaluated. A Cox regression model was constructed on the toxicity adjusted by the history of diabetes, age, pathological history, smoking history, calf circumference, physical activity, disability, falls, polypharmacy, frailty and vulnerability.

Results: 23.6% presented diabetes. The prevalence of frailty was 39.7%, vulnerability of 24.2% (G8) and 26.71% (VES-13). Frequent adverse effects were gastrointestinal (13.04%) and hematological (8.07%). Through the adjusted regression model type 2 diabetes mellitus, 3 or more comorbidities, history of tobacco use, calf circumference, physical activity, disability, falls, polypharmacy, vulnerability and frailty were significant factors.

Conclusion: The history of diabetes mellitus type 2 is a predictive factor for the risk of antineoplastic therapy toxicity in aged patients with prostate cancer.

Key words: diabetes mellitus, toxicity, antineoplastic, aged, cancer, prostate, cohort


Palabras clave

diabetes mellitus, toxicidad, quimioterapia, adultos mayores, cáncer, próstata, cohorte


Heidenreich A, Bastian P, Bellmunt J, Bolla M, Joniau S, Van Der Kwast T et al. EAU Guidelines on Porstate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent-Update 2013. European Urology [Internet]. 2014 [cited: 3/11/2018];65(1):124-137.Available from: https://www.europeanurology.com/article/S0302-2838(13)01040-3/fulltext

Heidenreich A, Bastian P, Bellmunt J, Bolla M, Joniau S, Van Der Kwast T et al. EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced Relapsing, and Castration-Resistant Prostate Cancer. European Urology [Internet]. 2014 [cited: 3/11/2018]; 65(2): 467-479. Available from:https://www.europeanurology.com/article/S0302-2838(13)01199-8/fulltext

Nieuweboer A, S. de Morrée E, M. de Graan A, Sparreboom A, De Wit R, Mathijssen R. Inter-patient variability in docetaxel pharmacokinetics: A review. Cancer Treat Rev [Internet]. 2015[cited: 3/11/2018]; 41(7):605-613. Available from : https://www.sciencedirect.com/science/article/pii/S030573721500081X

Burris H, Irvin R, Kuhn J, Kalter S, Smith L, Shaffer D et al. Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion. J Clin Oncol [Internet]. 1993[cited: 3/11/2018]; 11(5):950-958. Available from: http://ascopubs.org/doi/abs/10.1200/JCO.1993.11.5.950

Klepin H, Pitcher B, Ballman K, Kornblitch A, Hurria A, Winer E. Comorbidity, Chemotherapy Toxicity, and Outcomes Among Older Women Receiving Adjuvant Chemotherapy for Breast Cancer on a Clinical Trial: CALGB 49907 and CALGB 361004 (Alliance). J Oncol Pract [Internet]. 2014 [cited: 3/11/2018]; 10(5):e285-e292. Available from: http://ascopubs.org/doi/abs/10.1200/jop.2014.001388

Kalyani R, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. The Lancet Diabetes & Endocrinology [Internet]. 2014[cited: 3/11/2018]; 2(10):819-829. Available from: https://www.sciencedirect.com/science/article/pii/S2213858714700348

Tsilidis K, Kasimis K, Lopez D, Ntzani E, Ioannidis J. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. Bmj [Internet]. 2015 [cited: 3/11/2018];350:g7607. Available from: https://www.bmj.com/content/350/bmj.g7607

Runzer-Colmenares FM, Urrunaga-Pastor D, Aguirre LG, Reategui-Rivera CM, Parodi JF, Taype-Rondan A. Fragilidad y vulnerabilidad como predictores de radiotoxicidad en adultos mayores: un estudio longitudinal en Perú. Med Clin [Internet]. 2017[cited: 3/11/2018]; 149(8):325-330. Available from: https://www.sciencedirect.com/science/article/pii/S0025775317301860

US DEPARTMENT OF HEALTH AND HUMAN SERVICES. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), v4. 0. NIH Publication. 2017, no 09-5410.

Lilamand M, Kelaiditi E, Cesari M, Raynaud-Simon A, Ghisolfi A, Guyonnet S et al. Validation of the Mini Nutritional Assessment-Short Form in a population of frail elders without disability. Analysis of the Toulouse Frailty Platform population in 2013. J Nutr Health Aging [Internet]. 2015[cited: 3/11/2018]; 19(5):570-574. Available from: https://link.springer.com/article/10.1007/s12603-015-0457-4

Arnadottir S. Physical Activity Scale for the Elderly (PASE) to capture habitual physical activity patterns of older clients receiving health promoting visits. Physiotherapy [Internet]. 2016 [cited: 3/11/2018]; 102:e208. Available from: https://www.physiotherapyjournal.com/article/S0031-9406(16)30328-5/abstract

Collin C, Wade DT, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabil Studies [Internet]. 1988[cited: 3/11/2018]; 0:61-63. Available from: https://www.tandfonline.com/doi/abs/10.3109/09638288809164103

Wastesson J, Cedazo A, Fastbom J, Maioli S, Johnell K. The composition of polypharmacy: A registerbased study of Swedes aged 75 years and older. PloS one [Internet]. 2018 [cited: 3/11/2018]; 13(3):e0194892. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194892

Fried LP, Tangen C, Walston J, Newman A, Hirsch C, Gottdiener J et al. Frailty in Older Adults: Evidence for a Phenotype. J Gerontol Series A: Biological Sciences and Medical Sciences [Internet]. 2001[cited: 3/11/2018]; 56(3):M146-M157. Available from: https://academic.oup.com/biomedgerontology/article/56/3/M146/545770

Luciani A, Biganzoli L, Colloca G, Falci C, Castagneto B, Floriani I et al. Estimating the risk of chemotherapy toxicity in older patients with cancer: The role of the Vulnerable Elders Survey-13 (VES-13). J Geriatr Oncol [Internet]. 2015 [cited: 3/11/2018];6(4):272-279.Available from: https://www.sciencedirect.com/science/article/pii/S1879406815000521

Kanesvaran R, Zi-Ling O, Chan A, Krishna L, Tan T, Rajasekaran T et al. 539P The use of G8 as a screening tool in a tertiary Asian cancer centre. Ann Oncol [Internet]. 2016[cited: 3/11/2018]; 27(9). Available from: https://academic.oup.com/annonc/article/27/suppl_9/mdw599.018/2920096

Fraenkel M, Ketzinel-Gilad M, Ariav Y, Pappo O, Karaca M, Castel J et al. mTOR Inhibition by Rapamycin Prevents β-Cell Adaptation to Hyperglycemia and Exacerbates the Metabolic State in Type 2 Diabetes. Diabetes [Internet]. 2008[cited: 3/11/2018]; 57(4):945-957. Available from: http://diabetes.diabetesjournals.org/content/57/4/945.short

Tannock I, De Wit R, Berry W, Horti J, Pluzanska A, Oudard S et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med [Internet]. 2004[cited: 3/11/2018]; 351(15):1502-1512. Available from: https://www.nejm.org/doi/full/10.1056/nejmoa040720

Du Y, Rayner C, Jones K, Talley N, Horowitz M. Gastrointestinal Symptoms in diabetes: prevalence, assessment, pathogenesis, and management. Diabetes Care [Internet]. 2018 [cited: 3/11/2018]; 41(3):627-637. Available from: http://care.diabetesjournals.org/content/41/3/627

Lutz S, Hennenlotter J, Scharpf M, Sailer C, Fritsche L, Schmid V et al. Androgen receptor overexpression in prostate cancer in type 2 diabetes. Molecular Metabolism [Internet]. 2018[cited: 3/11/2018]; 8:158-166. Available from: https://www.sciencedirect.com/science/article/pii/S2212877817306841

Abizanda P, Romero L, Sanchez-Jurado PM, Martinez-Reig M, Alfonso-Silguero SA, Rodriguez-Manas L. Age, frailty, disability, institutionalization, multimorbidity or comorbidity. Which are the main targets in older adults? The Journal of Nutrition, Health & Aging [Internet]. 2014[cited: 3/11/2018]; 18(6):622. Available from: https://link.springer.com/article/10.1007/s12603-014-0033-3

Bechis SK, Carroll PR, Cooperberg MR. Impact of Age at Diagnosis on Prostate Cancer Treatment and Survival. J Clin Oncol [Internet]. 2011[cited: 3/11/2018]; 29(2):235-241. Available from:


Thompson IM, Ankerst DP, Chi C, Goodman P, Tangen C, Scott M et al. Assessing Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial. JNCI J Natl Cancer Inst [Internet]. 2006[cited: 3/11/2018]; 98(8):529-534. Available from: https://academic.oup.com/jnci/article/98/8/529/2522069

Menon A, Handattu S, Shetty J, Shanmukha B. Study of cutaneous adverse effects of cancer chemotherapy. Clin Dermatol Rev [Internet]. 2018[cited: 3/11/2018]; 2(1):19. Available from: http://www.cdriadvlkn.org/article.asp?issn=2542-551X;year=2018;volume=2;issue=1;spage=19;epage=24;aulast=Menon

Galbraith G, Pandey J. Tumor necrosis factor alpha (TNF-α) gene polymorphism in alopecia areata. Human Genetics [Internet]. 1995[cited: 3/11/2018]; 96(4):433-436. Available from: https://link.springer.com/article/10.1007/BF00191802

Gosney M. Clinical assessment of elderly people with cancer. The Lancet Oncology [Internet]. 2005[cited: 3/11/2018]; 6(10):790-797. Available from: https://www.sciencedirect.com/science/article/pii/S1470204505703892

Angulo J, El Assar M, Rodríguez-Mañas L. Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. Mol Aspects Med [Internet]. 2016[cited: 3/11/2018]; 50:1-32. Available from: https://www.sciencedirect.com/science/article/pii/S0098299716300097

Decoster L, Van Puyvelde K, Mohile S, Wedding U, Basso U, Colloca G et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol [Internet]. 2014[cited: 3/11/2018]; 26(2):288-300. Available from: https://academic.oup.com/annonc/article/26/2/288/2800578