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Prognostic impact of polypharmacy and drug interactions in patients with advanced cancer

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Abstract

The risk of potential drug–drug interactions (PDI) is poorly studied in oncology. We included 105 patients with advanced non-small-cell lung cancer (NSCLC), 100 patients with advanced breast cancer (BC) and 100 patients of the palliative care unit (PCU) receiving systemic palliative treatment between 2010 and 2015. All patients suffered from advanced incurable cancer and received basic palliative care. PDI were assessed using the hospINDEX of all drugs approved in Switzerland in combination with a specific drug interaction software. Primary study objective was to assess the prognostic impact of PDI per patient cohort using Kaplan–Meier statistics. The median number of comedications was 5 (range 0–15). Major-risk PDI were detected in 74 patients (24.3%). The number of comedications was significantly associated with PDI (p < 0.0001). Major-risk PDI increased from 14% in patients with < 4 comedications to 24% in patients with 4–7 comedications, 40% with 8–11 comedications and 67% in patients with > 11 comedications. Median overall survival (OS) was 8.6 months in NSCLC, 33 months in BC and 1.2 months in PCU patients. PDI were significantly associated with inferior OS in BC (HR = 1.32, 95% CI 1.01–1.74, p = 0.049), but not in NSCLC (HR = 1.11, 95% CI 0.84–1.47, p = 0.45) or PCU (HR = 1.12, 95% CI 0.86–1.45, p = 0.41). PDI remained significantly associated with OS in BC (HR = 1.32, p = 0.049) in the adjusted model. In conclusion, PDI are frequent in patients with advanced cancer and increased caution with polypharmacy is warranted when treating such patients.

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References

  1. Beijnen JH, Schellens JH (2004) Drug interactions in oncology. Lancet Oncol 5(8):489–496. https://doi.org/10.1016/S1470-2045(04)01528-1

    Article  CAS  PubMed  Google Scholar 

  2. Scripture CD, Figg WD (2006) Drug interactions in cancer therapy. Nat Rev Cancer 6(7):546–558. https://doi.org/10.1038/nrc1887

    Article  CAS  PubMed  Google Scholar 

  3. McLeod HL (1997) Therapeutic drug monitoring opportunities in cancer therapy. Pharmacol Ther 74(1):39–54

    Article  CAS  PubMed  Google Scholar 

  4. Ratz Bravo AE, Tchambaz L, Krahenbuhl-Melcher A, Hess L, Schlienger RG, Krahenbuhl S (2005) Prevalence of potentially severe drug–drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Drug Saf 28(3):263–275

    Article  PubMed  Google Scholar 

  5. Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T (2015) The rising tide of polypharmacy and drug–drug interactions: population database analysis 1995–2010. BMC Med 13:74. https://doi.org/10.1186/s12916-015-0322-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Leucuta SE, Vlase L (2006) Pharmacokinetics and metabolic drug interactions. Curr Clin Pharmacol 1(1):5–20

    Article  CAS  PubMed  Google Scholar 

  7. Yoshida K, Maeda K, Sugiyama Y (2013) Hepatic and intestinal drug transporters: prediction of pharmacokinetic effects caused by drug–drug interactions and genetic polymorphisms. Annu Rev Pharmacol Toxicol 53:581–612. https://doi.org/10.1146/annurev-pharmtox-011112-140309

    Article  CAS  PubMed  Google Scholar 

  8. Zhang H, Davis CD, Sinz MW, Rodrigues AD (2007) Cytochrome P450 reaction-phenotyping: an industrial perspective. Expert Opin Drug Metab Toxicol 3(5):667–687. https://doi.org/10.1517/17425255.3.5.667

    Article  CAS  PubMed  Google Scholar 

  9. Ramos-Esquivel A, Viquez-Jaikel A, Fernandez C (2017) Potential drug–drug and herb–drug interactions in patients with cancer: a prospective study of medication surveillance. J Oncol Pract. https://doi.org/10.1200/JOP.2017.020859

    Article  PubMed  Google Scholar 

  10. Segal EM, Flood MR, Mancini RS, Whiteman RT, Friedt GA, Kramer AR, Hofstetter MA (2014) Oral chemotherapy food and drug interactions: a comprehensive review of the literature. J Oncol Pract 10(4):e255–e268. https://doi.org/10.1200/JOP.2013.001183

    Article  PubMed  Google Scholar 

  11. Kang SP, Ratain MJ (2010) Inconsistent labeling of food effect for oral agents across therapeutic areas: differences between oncology and non-oncology products. Clin Cancer Res 16(17):4446–4451. https://doi.org/10.1158/1078-0432.CCR-10-0663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Szmulewitz RZ, Ratain MJ (2013) Playing Russian roulette with tyrosine kinase inhibitors. Clin Pharmacol Ther 93(3):242–244. https://doi.org/10.1038/clpt.2012.245

    Article  CAS  PubMed  Google Scholar 

  13. Riechelmann RP, Del Giglio A (2009) Drug interactions in oncology: how common are they? Ann Oncol 20(12):1907–1912. https://doi.org/10.1093/annonc/mdp369

    Article  CAS  PubMed  Google Scholar 

  14. Peters S, Zimmermann S, Adjei AA (2014) Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: comparative pharmacokinetics and drug–drug interactions. Cancer Treatm Rev 40(8):917–926. https://doi.org/10.1016/j.ctrv.2014.06.010

    Article  CAS  Google Scholar 

  15. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG (2014) Drug–drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 15(8):e315–e326. https://doi.org/10.1016/S1470-2045(13)70579-5

    Article  CAS  PubMed  Google Scholar 

  16. Riechelmann RP, Zimmermann C, Chin SN, Wang L, O’Carroll A, Zarinehbaf S, Krzyzanowska MK (2008) Potential drug interactions in cancer patients receiving supportive care exclusively. J Pain Symptom Manag 35(5):535–543. https://doi.org/10.1016/j.jpainsymman.2007.06.009

    Article  Google Scholar 

  17. Ussai S, Petelin R, Giordano A, Malinconico M, Cirillo D, Pentimalli F (2015) A pilot study on the impact of known drug–drug interactions in cancer patients. J Exp Clin Cancer Res 34:89. https://doi.org/10.1186/s13046-015-0201-2

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yeoh TT, Tay XY, Si P, Chew L (2015) Drug-related problems in elderly patients with cancer receiving outpatient chemotherapy. J Geriatr Oncol 6(4):280–287. https://doi.org/10.1016/j.jgo.2015.05.001

    Article  PubMed  Google Scholar 

  19. Ussai S, Sparta MC (2014) Adverse drug events: how information technology will meet the challenges of pharmacovigilance. Value Health 17(7):A750. https://doi.org/10.1016/j.jval.2014.08.193

    Article  CAS  PubMed  Google Scholar 

  20. McCune JS, Hatfield AJ, Blackburn AA, Leith PO, Livingston RB, Ellis GK (2004) Potential of chemotherapy–herb interactions in adult cancer patients. Support Care Cancer 12(6):454–462. https://doi.org/10.1007/s00520-004-0598-1

    Article  PubMed  Google Scholar 

  21. Popa MA, Wallace KJ, Brunello A, Extermann M, Balducci L (2014) Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy. J Geriatr Oncol 5(3):307–314. https://doi.org/10.1016/j.jgo.2014.04.002

    Article  PubMed  PubMed Central  Google Scholar 

  22. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173(6):676–682. https://doi.org/10.1093/aje/kwq433

    Article  PubMed  Google Scholar 

  23. Karlen S, Eschmann E, Blaser J (2014) Entscheidungsunterstützung beim Medikamentenprozess: Wie umfangreich sind die hospINDEX-Stammdaten? Swiss Med Inf 30

  24. van Leeuwen RW, Swart EL, Boven E, Boom FA, Schuitenmaker MG, Hugtenburg JG (2011) Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method. Ann Oncol 22(10):2334–2341. https://doi.org/10.1093/annonc/mdq761

    Article  PubMed  Google Scholar 

  25. Voll ML, Yap KD, Terpstra WE, Crul M (2010) Potential drug–drug interactions between anti-cancer agents and community pharmacy dispensed drugs. Pharm World Sci 32(5):575–580. https://doi.org/10.1007/s11096-010-9410-0

    Article  CAS  PubMed  Google Scholar 

  26. Bulsink A, Imholz AL, Brouwers JR, Jansman FG (2013) Characteristics of potential drug-related problems among oncology patients. Int J Clin Pharm 35(3):401–407. https://doi.org/10.1007/s11096-012-9747-7

    Article  PubMed  Google Scholar 

  27. Kruse V, Somers A, Van Bortel L, De Both A, Van Belle S, Rottey S (2014) Sunitinib for metastatic renal cell cancer patients: observational study highlighting the risk of important drug–drug interactions. J Clin Pharm Ther 39(3):259–265. https://doi.org/10.1111/jcpt.12134

    Article  CAS  PubMed  Google Scholar 

  28. Fernandez de Palencia Espinosa MA, Diaz Carrasco MS, Fuster Soler JL, Ruiz Merino G, De la Rubia Nieto MA, Espuny Miro A (2014) Pharmacoepidemiological study of drug–drug interactions in onco-hematological pediatric patients. Int J Clin Pharm 36(6):1160–1169. https://doi.org/10.1007/s11096-014-0011-1

    Article  CAS  PubMed  Google Scholar 

  29. Stoll P, Kopittke L (2015) Potential drug–drug interactions in hospitalized patients undergoing systemic chemotherapy: a prospective cohort study. Int J Clin Pharm 37(3):475–484. https://doi.org/10.1007/s11096-015-0083-6

    Article  CAS  PubMed  Google Scholar 

  30. Rompelman FM, Smit AA, Franssen EJ, Crul M (2016) Drug–drug interactions of cytostatics with regular medicines in lung cancer patients. J Oncol Pharm Pract. https://doi.org/10.1177/1078155216664200

    Article  PubMed  Google Scholar 

  31. Alsanad SM, Howard RL, Williamson EM (2016) An assessment of the impact of herb–drug combinations used by cancer patients. BMC Complement Altern Med 16(1):393. https://doi.org/10.1186/s12906-016-1372-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Keller KL, Franquiz MJ, Duffy AP, Trovato JA (2016) Drug–drug interactions in patients receiving tyrosine kinase inhibitors. J Oncol Pharm Pract. https://doi.org/10.1177/1078155216682311

    Article  PubMed  Google Scholar 

  33. Balk TE, van der Sijs IH, van Gelder T, Janssen JJB, van der Sluis IM, van Leeuwen RWF, Engels FK (2017) Drug–drug interactions in pediatric oncology patients. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.26410

    Article  PubMed  Google Scholar 

  34. Meek IL, Vonkeman HE, Kasemier J, Movig KL, van de Laar MA (2013) Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: a placebo-controlled, ex vivo, serial placebo-controlled serial crossover study. Eur J Clin Pharmacol 69(3):365–371. https://doi.org/10.1007/s00228-012-1370-y

    Article  CAS  PubMed  Google Scholar 

  35. Martinez-Moreno R, Aguilar M, Wendl C, Bazner H, Ganslandt O, Henkes H (2016) Fatal thrombosis of a flow diverter due to ibuprofen-related antagonization of acetylsalicylic acid. Clin Neuroradiol 26(3):355–358. https://doi.org/10.1007/s00062-015-0487-7

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany

    Alexander Hoemme & Holger Barth

  2. Department of Medical Oncology and Hematology, Cantonal Hospital, St. Gallen, Switzerland

    Alexander Hoemme, Florian Strasser, Martin Früh, Christoph Driessen & Markus Joerger

  3. Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Manuel Haschke

  4. Institute of Pharmacology, University of Bern, Bern, Switzerland

    Manuel Haschke

  5. Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland

    Stephan Krähenbühl

  6. Hospital Pharmacy, Cantonal Hospital, St. Gallen, Switzerland

    Claudia Lehner

  7. Department of Information Technology, Cantonal Hospital, St. Gallen, Switzerland

    Alexander von Kameke

  8. HCI Solutions Inc., Bern, Switzerland

    Thomas Wälti

  9. Breast Center, Cantonal Hospital, St. Gallen, Switzerland

    Beat Thürlimann

  10. Medical Oncology and Clinical Pharmacology, Cantonal Hospital, Rorschacherstr. 95, 9007, St. Gallen, Switzerland

    Markus Joerger

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  1. Alexander Hoemme
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Hoemme, A., Barth, H., Haschke, M. et al. Prognostic impact of polypharmacy and drug interactions in patients with advanced cancer. Cancer Chemother Pharmacol 83, 763–774 (2019). https://doi.org/10.1007/s00280-019-03783-9

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  • DOI: https://doi.org/10.1007/s00280-019-03783-9

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