The association of ABCC5 and ABCC11 polymorphisms with the pharmacokinetics of 5-FU in advanced gastric cancer patients

Yıl 2020, Cilt: 10 Sayı: 3, 285 - 291, 29.09.2020

Zeliha Pala Kara , Ezgi Oztas Dilek Ozturk , Yasemin Akyel Zeynep Turna , Alper Okyar Gül Özhan

https://doi.org/10.33808/clinexphealthsci.757619

Öz

Objective: Gastric cancer is the second leading cause of cancer-related death worldwide. 5-Fluorouracil (5-FU) is one of the most commonly used drugs to treat cancer, but 5-FU and its forms are characterized by wide inter-individual pharmacokinetic variability. ABCC5 and ABCC11 are members of the ABC transporter superfamily and play a role in the efflux of antineoplastic drugs like 5-FU.
Methods: The influence of two SNPs in ABCC5 (rs562, T>C) and ABCC11 (rs17822931, G>A) was evaluated based on the pharmacokinetics and toxicity of 5-FU in HER2-negative advanced gastric cancer patients treated with cisplatin and 5-FU (n=18). The genetic variants and plasma 5-FU concentrations were detected by RT-PCR and HPLC, respectively.
Results: There was no statistically significant difference between 5-FU AUC0-96 h values and ABCC5 (rs562; T>C), 21.04 ±3.46 vs 16.65 μg.h/mL, p=0,261) and ABCC11 (rs17822931; G>A), 17.04 ±4.39 vs 54 ±3.79 mg.h/L, p=0,564) variants. Similarly, there were no statistically significant differences between the variants and the most frequently observed side effects of diarrhea and mucositis.
Conclusion: We recommend investigating the noted SNPs more precisely in a larger study population with more comprehensive evaluation.

Anahtar Kelimeler

ABCC5, ABCC11, 5-FU, Pharmacogenetics, Gastric cancer

Destekleyen Kurum

Scientific Research Projects Coordination Unit of Istanbul University

Proje Numarası

25139 and 24985

Kaynakça

• [1] Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 2010; 376(9742): 687-97.
• [2] Power DG, Kelsen DP, Shah MA. Advanced gastric cancer - Slow but steady progress. Cancer Treat. Rev. 2010; 36(5): 384-92.
• [3] Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 1996; 7(6): 593-600.
• [4] Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat. Rev. Cancer. 2003; 3(5): 330-8.
• [5] Cancer (American Cancer Society). Learn about cancer. Stomach Cancer. Detailed Guide. October 2, 2016; Available at: http://www.cancer.org/cancer/stomachcancer/detailedguide/index. Accessed October 15, 2016
• [6] Saif MW, Choma A, Salamone SJ, Chu E. Pharmacokinetically guided dose adjustment of 5-fluorouracil: A rational approach to improving therapeutic outcomes. J. Natl. Cancer Inst. 2009; 101(22): 1543-52.
• [7] Kaldate RR, Haregewoin A, Grier CE, Hamilton SA, McLeod HL. Modeling the 5-Fluorouracil Area Under the Curve Versus Dose Relationship to Develop a Pharmacokinetic Dosing Algorithm for Colorectal Cancer Patients Receiving FOLFOX6. Oncologist 2012; 17(3): 296-302.
• [8] Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M. Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: Results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 2099–2105.
• [9] Beumer JH, Chu E, Allegra C, Tanigawara Y, Milano G, Diasio R, Kim TW, Mathijssen RH, Zhang L, Arnold D, Muneoka K, Boku N, Joerger M. Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5-Fluorouracil Therapy. Clin Pharmacol Ther 2019; 105: 598–613.
• [10] Lee JJ, Beumer JH, Chu E. Therapeutic drug monitoring of 5-fluorouracil. Cancer Chemother. Pharmacol. 2016; 78: 447–464.
• [11] Freeman K, Saunders MP, Uthman OA, Taylor-Phillips S, Connock M, Court R, Gurung T, Sutcliffe P, Clarke A. Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review. BMC Cancer 2016; 16: 523.
• [12] Pratt S, Shepard RL, Kandasamy RA, Johnston PA, Perry W, Dantzig AH. The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol Cancer Ther 2005; 4: 855–863.
• [13] Uemura T, Oguri T, Maeno K, Sone K, Takeuchi A, Fukuda S, Kunii E, Takakuwa O, Kanemitsu Y, Ohkubo H, Takemura M, Ito Y, Niimi A. ABCC11 gene polymorphism as a potential predictive biomarker for an oral 5-fluorouracil derivative drug S-1 treatment in non-small cell lung cancer. Cancer Chemother Pharmacol 2019; 84: 1229–1239. [14] Hamzic S, Wenger N, Froehlich TK, Joerger M, Aebi S, Largiadèr CR, Amstutz U. The impact of ABCC11 polymorphisms on the risk of early-onset fluoropyrimidine toxicity. Pharmacogenomics J 2017; 17: 319–324.
• [15] Nies AT, Magdy T, Schwab M, Zanger UM. Role of ABC Transporters in Fluoropyrimidine-Based Chemotherapy Response. Adv Cancer Res . 2015; 125: 217-43. [16] Öztaş E, Parejo Garcia-Saavedra A, Yanar F, Özçinar B, Aksakal N, Purisa S, Özhan G. P-glycoprotein polymorphism and levothyroxine bioavailability in hypothyroid patients. Saudi Pharm J 2018; 26: 274–278.
• [17] Casale F, Canaparo R, Muntoni E, Serpe L, Zara GP, Della Pepa C, Berno E, Costa M, Eandi M. Simultaneous HPLC determination of 5-fluorouracil and its metabolites in plasma of cancer patients. Biomed Chromatogr 2002 ;16: 446–452.
• [18] Beumer JH, Chu E, Allegra C, Tanigawara Y, Milano G, Diasio R, Kim TW, Mathijssen RH, Zhang L, Arnold D, Muneoka K, Boku N, Joerger M. Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5-Fluorouracil Therapy. Clin Pharmacol Ther 2019; 105: 598–613.
• [19] Fleming GF, Schumm P, Friberg G, Ratain MJ, Njiaju UO, Schilsky RL. Circadian variation in plasma 5-fluorouracil concentrations during a 24 hour constant-rate infusion. BMC Cancer 2015; 15: 69-77. [20] Kuwahara A, Kobuchi S, Tamura T. Association between circadian and chemotherapeutic cycle effects on plasma concentration of 5-fluorouracil and the clinical outcome following definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in patients with esophageal squamous cell carcinoma. Oncol Lett 2019; 17: 668–675.
• [21] Metzger G, Massari C, Etienne M, Comisso M, Brienza S, Touitou Y, Milano G, Bastian G, Et J, Levi F. Spontaneous or imposed circadian changes in plasma concentrations of 5-fluorouracil coadministered with folinic acid and oxaliplatin: Relationship with mucosal toxicity in patients with cancer. Clin Pharmacol Ther 1994; 56: 190–201.
• [22] Teft WA, Welch S, Lenehan J, Parfitt J, Choi YH, Winquist E, Kim RB. OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy. Br J Cancer 2015; 112: 857–865.
• [23] Lal S, Sutiman N, Ooi LL, Wong ZW, Wong NS, Ang PCS, Chowbay B. Pharmacogenetics of ABCB5, ABCC5 and RLIP76 and doxorubicin pharmacokinetics in Asian breast cancer patients. Pharmacogenomics J 2017; 17: 337–343.
• [24] Yoshiura KI, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, Bannai M, Tokunaga K, Sonoda S, Komaki R, Ihara M, Saenko VA, Alipov GK, Sekine I, Komatsu K, Takahashi H, Nakashima M, Sosonkina N, Mapendano CK, Ghadami M, Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray JC, Saito S, Nakamura Y, Niikawa N. A SNP in the ABCC11 gene is the determinant of human earwax type. Nat Genet 2006; 38: 324–330.
• [25] Ishikawa T, Toyoda Y, Yoshiura KI, Niikawa N. Pharmacogenetics of human ABC transporter ABCC11: New insights into apocrine gland growth and metabolite secretion. Front. Genet. 2013; 3: 306-319.
• [26] Freeman K, Connock M, Cummins E, Al. E. Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Health Technology Assessment 2015; 19(91): 1-321.
• [27] Meta-analysis Group In Cancer, Piedbois P, Rougier P, Buyse M, Pignon J, Ryan L, Hansen R, Zee B, Weinerman B, Pater J, Leichman C, Macdonald J, Benedetti J, Lokich J, Fryer J, Brufman G, Isacson R, Laplanche A, E. L. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998; 16: 301–308.