Evaluation of drug-drug interactions in patients receiving FOLFOX chemotherapy: A prospective study

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Abstract

Aim. To evaluate the frequency and clinical significance of drug-drug interactions (DDI) in patients receiving drug antitumor therapy using the Drugs® and Medscape® DDI calculators.

Materials and methods. The study included 282 patients with a mean age of 65 years (36–84) who received FOLFOX chemotherapy, of whom 151 (53%) were males and 131 (47%) were females. At the start of the first course of chemotherapy, 214 (75%) patients were receiving concomitant therapy on a regular basis.

Results. The odds of severe toxicity in patients receiving concomitant therapy were 2.720 times higher [95% confidence interval (CI) 1.025–7.218; p=0.038]. Patients with strong DDI were statistically significantly more likely to develop mucositis after the first course of drug antitumor therapy: 14 (38.9%) vs 36 (20.2%) according to Drugs®, p=0.041; 22 (33.3%) vs 28 (18.9%) according to Medscape®; p=0.036. Similar results were obtained in a subgroup of patients at risk of QT prolongation according to Drugs® – 10 (52.6%) vs 40 (20.5%); p<0.001. Patients taking calcium channel blockers were statistically significantly more likely to develop dose-limiting toxicity: 18 (40.9%) vs 52 (21.8%). The odds of dose-limiting toxicity were 2.476 times higher: 95% CI 1.261–4.864; p=0.007.

Conclusion. The incidence of DDI in patients with gastrointestinal tumors receiving FOLFOX best supportive therapy can be as high as 90.2%, with one in three DDI classified as serious. Drugs® and Medscape® DDI services cover only 80% of concomitant medications and are not adapted to oncology, necessitating the development of more versatile approaches.

About the authors

Denis S. Fedorinov

Petrovsky National Research Center of Surgery; Moscow Multidisciplinary Clinical Center "Kommunarka"; Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: deni_fe@mail.ru
ORCID iD: 0000-0001-5516-7367
SPIN-code: 1079-8460

Oncologist

Russian Federation, Moscow; Moscow; Moscow

Marina A. Lyadova

Moscow State Budgetary Healthcare Institution «Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department»; Novokuznetsk State Institute for Further Training of Physicians Branch Campus of the Russian Medical Academy of Continuous Professional Education

Email: deni_fe@mail.ru
ORCID iD: 0000-0002-9558-5579
SPIN-code: 8220-2854

Cand. Sci. (Med.)

Russian Federation, Moscow; Novokuznetsk

Vladimir K. Lyadov

Russian Medical Academy of Continuous Professional Education; Moscow State Budgetary Healthcare Institution «Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department»; Novokuznetsk State Institute for Further Training of Physicians Branch Campus of the Russian Medical Academy of Continuous Professional Education

Email: deni_fe@mail.ru
ORCID iD: 0000-0002-7281-3591
SPIN-code: 5385-7889

D. Sci. (Med.)

Russian Federation, Moscow; Moscow; Novokuznetsk

Dmitry A. Sychev

Petrovsky National Research Center of Surgery; Russian Medical Academy of Continuous Professional Education

Email: deni_fe@mail.ru
ORCID iD: 0000-0002-4496-3680
SPIN-code: 4525-7556

D. Sci. (Med.), Prof., Acad. RAS

Russian Federation, Moscow; Moscow

References

  1. Surveillance, Epidemiology, and End Results Program (SEER). Available at: https://seer.cancer.gov/ Assecced: 20.02.2025.
  2. Yang L, Liu S, Xiong Z, et al. Changes in colorectal cancer incidence by site and age from 1973 to 2015: a SEER database analysis. Aging Clin Exp Res. 2021;33(7):1937-46. doi: 10.1007/s40520-020-01721-x
  3. Balducci L, Goetz-Parten D, Steinman MA. Polypharmacy and the management of the older cancer patient. Ann Oncol. 2013;24:vii36-40. doi: 10.1093/annonc/mdt266
  4. Extermann M. Interaction between Comorbidity and Cancer. Cancer Control. 2007;14(1):13-22. doi: 10.1177/107327480701400103
  5. Ramsdale E, Lemelman T, Loh KP, et al. Geriatric assessment-driven polypharmacy discussions between oncologists, older patients, and their caregivers. J Geriatr Oncol. 2018;9(5):534-9. doi: 10.1016/j.jgo.2018.02.007
  6. Scott IA, Hilmer SN, Reeve E, et al. Reducing Inappropriate Polypharmacy: The Process of Deprescribing. JAMA Intern Med. 2015;175(5):827. doi: 10.1001/jamainternmed.2015.0324
  7. Riechelmann R, Girardi D. Drug interactions in cancer patients: A hidden risk? J Res Pharm Pract. 2016;5(2):77-8. doi: 10.4103/2279-042X.179560
  8. Clark LT, Watkins L, Piña IL, et al. Increasing Diversity in Clinical Trials: Overcoming Critical Barriers. Curr Probl Cardiol. 2019;44(5):148-72. doi: 10.1016/j.cpcardiol.2018.11.002
  9. Mohamed MR, Mohile SG, Juba KM, et al. Association of polypharmacy and potential drug-drug interactions with adverse treatment outcomes in older adults with advanced cancer. Cancer. 2023;129(7):1096-104. doi: 10.1002/cncr.34642
  10. Приказ Минздравсоцразвития России от 22.11.2010 №1022н «Об утверждении Порядка оказания медицинской помощи населению по профилю „Клиническая фармакология“». Режим доступа: http://www.rg.ru/2010/12/31/farmakologia-dok.html. Ссылка доступна на 20.02.2025 [Prikaz Minzdravsotsrazvitiia Rossii ot 22.11.2010 No 1022n «Ob utverzhdenii Poriadka okazaniia meditsinskoi pomoshchi naseleniiu po profiliu „Klinicheskaia farmakologiia“». Available at: http://www.rg.ru/2010/12/31/farmakologia-dok.html. Accessed: 20.02.2025.
  11. Сычев Д.А., Отделенов В.А. Межлекарственные взаимодействия в практике интерниста: взгляд клинического фармаколога. Справочник поликлинического врача. 2014;12:18-21. Режим доступа: https://omnidoctor.ru/library/izdaniya-dlya-vrachey/spravochnik-poliklinicheskogo-vracha/spv2014/spv2014_12/mezhlekarstvennye-vzaimodeystviya-v-praktike-internista-vzglyad-klinicheskogo-farmakologa/ Ссылка доступна на 20.02.2025 [Sychev DA, Otdelenov VA. Mezhlekarstvennye vzaimodeistviia v praktike internista: vzgliad klinicheskogo farmakologa. Spravochnik poliklinicheskogo vracha. 2014;12:18-21. Available at: https://omnidoctor.ru/library/izdaniya-dlya-vrachey/spravochnik-poliklinicheskogo-vracha/spv2014/spv2014_12/mezhlekarstvennye-vzaimodeystviya-v-praktike-internista-vzglyad-klinicheskogo-farmakologa/ Accessed: 20.02.2025 (in Russian)].
  12. Drug Interaction Checker. Available at: https://www.drugs.com/drug_interactions.html. Accessed: 20.02.2025.
  13. Medscape Drug Interaction Checker. Available at: https://reference.medscape.com/drug-interactionchecker. Accessed: 20.02.2025.
  14. Ungureanu D, Popa A, Nemeș A, Crișan CA. Concomitant Administration of Psychotropic and Prostate Cancer Drugs: A Pharmacoepidemiologic Study Using Drug–Drug Interaction Databases. Biomedicines. 2024;12(9):1971. doi: 10.3390/biomedicines12091971
  15. Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Published: November 27. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed: 20.02.2025.

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