Skip to main content
SpringerLink
Log in

Transient elevation of serum cystatin C concentrations during perioperative cisplatin-based chemotherapy in esophageal cancer patients

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

In the present study, the time–concentration profile of platinum (Pt) in plasma was compared to that of serum cystatin C (Cys C) in Japanese esophageal cancer patients receiving perioperative cisplatin-based chemotherapy.

Methods

Five male and one female patients receiving 2 successive cycles of cisplatin-based chemotherapy combined with 5-fluorouracil, the treatment for esophageal squamous cell carcinoma, participated in this study. The pharmacokinetic parameters in each patient were calculated from the individual plasma Pt concentration–time curve after intravenous infusion of cisplatin using the one-compartment model.

Results

Within a week of starting the first cycle of chemotherapy, serum Cys C concentrations increased in all patients from 122.6 to 143.0 %, subsequently returning to baseline levels in approximately 10 days. A similar increase in serum Cys C levels also occurred during the second treatment cycle. However, no increase in serum creatinine levels was observed during either treatment cycle. In addition, the concentration of plasma Pt 2 days after treatment in the first and second cycles did not correlate with those of either serum Cys C or creatinine. Finally, the half-life of Pt in plasma during the first treatment cycle was not significantly different from that in the second cycle.

Conclusions

These findings suggest that concentration fluctuations in serum Cys C are unlikely to correlate with Pt elimination from the plasma and that renal function estimates based on serum Cys C concentration might be underestimated during perioperative cisplatin-based chemotherapy for esophageal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Madias NE, Harrington JT (1978) Platinum nephrotoxicity. Am J Med 65(2):307–314

    Article  PubMed  CAS  Google Scholar 

  2. Kintzel PE, Dorr RT (1995) Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev 21(1):33–64

    Article  PubMed  CAS  Google Scholar 

  3. Filler G, Bokenkamp A, Hofmann W, Le Bricon T, Martinez-Bru C, Grubb A (2005) Cystatin C as a marker of GFR—history, indications, and future research. Clin Biochem 38(1):1–8

    Article  PubMed  CAS  Google Scholar 

  4. Newman DJ (2002) Cystatin C. Ann Clin Biochem 39(Pt 2):89–104

    Article  PubMed  CAS  Google Scholar 

  5. Chew JS, Saleem M, Florkowski CM, George PM (2008) Cystatin C—a paradigm of evidence based laboratory medicine. Clin Biochem Rev 29(2):47–62

    PubMed  Google Scholar 

  6. Schmitt A, Gladieff L, Lansiaux A, Bobin-Dubigeon C, Etienne-Grimaldi MC, Boisdron-Celle M, Serre-Debauvais F, Pinguet F, Floquet A, Billaud E, Le Guellec C, Penel N, Campone M, Largillier R, Capitain O, Fabbro M, Houede N, Medioni J, Bougnoux P, Lochon I, Chatelut E (2009) A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients. Clin Cancer Res 15(10):3633–3639

    Article  PubMed  CAS  Google Scholar 

  7. Tanaka A, Aiba T, Otsuka T, Suemaru K, Nishimiya T, Inoue T, Murase M, Kurosaki Y, Araki H (2010) Population pharmacokinetic analysis of vancomycin using serum cystatin C as a marker of renal function. Antimicrob Agents Chemother 54(2):778–782

    Article  PubMed  CAS  Google Scholar 

  8. Nagai N, Kinoshita M, Ogata H, Tsujino D, Wada Y, Someya K, Ohno T, Masuhara K, Tanaka Y, Kato K, Nagai H, Yokoyama A, Kurita Y (1996) Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity after intravenous infusions of cisplatin to cancer patients. Cancer Chemother Pharmacol 39(1–2):131–137

    Article  PubMed  CAS  Google Scholar 

  9. Benohr P, Grenz A, Hartmann JT, Muller GA, Blaschke S (2006) Cystatin C—a marker for assessment of the glomerular filtration rate in patients with cisplatin chemotherapy. Kidney Blood Press Res 29(1):32–35

    Article  PubMed  CAS  Google Scholar 

  10. Bárdi E, Bobok I, Oláh AV, Oláh E, Kappelmayer J, Kiss C (2004) Cystatin C is a suitable marker of glomerular function in children with cancer. Pediatr Nephrol 19(10):1145–1147

    Article  PubMed  Google Scholar 

  11. Štabuc B, Vrhovec L, Štabuc-Šilih M, Cizej TE (2000) Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy. Clin Chem 46(2):193–197

    PubMed  Google Scholar 

  12. Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, Ikeda K, Kanda T, Tsujinaka T, Nakamura K, Fukuda H (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19:68–74

    Google Scholar 

  13. Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W, Watanabe H, Isono K, Aoyama N, Makuuchi H, Tanaka O, Yamana H, Ikeuchi S, Kabuto T, Nagai K, Shimada Y, Kinjo Y, Fukuda H (2003) Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study—JCOG9204. J Clin Oncol 21(24):4592–4596

    Article  PubMed  Google Scholar 

  14. Adhim Z, Lin X, Huang W, Morishita N, Nakamura T, Yasui H, Otsuki N, Shigemura K, Fujisawa M, Nibu K, Shirakawa T (2012) E10A, an adenovirus carrying endostatin gene, dramatically increased the tumor drug concentration of metronomic chemotherapy with low-dose cisplatin in a xenograft mouse model for head and neck squamous cell carcinoma. Cancer Gene Ther 19:144–152

    Google Scholar 

  15. Yamaoka K, Tanigawara Y, Nakagawa T, Uno T (1981) A pharmacokinetic analysis program (multi) for microcomputer. J Pharmacobiodyn 4(11):879–885

    Article  PubMed  CAS  Google Scholar 

  16. Hoek FJ, Kemperman FA, Krediet RT (2003) A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant 18(10):2024–2031

    Article  PubMed  CAS  Google Scholar 

  17. Keevil BG, Kilpatrick ES, Nichols SP, Maylor PW (1998) Biological variation of cystatin C: implications for the assessment of glomerular filtration rate. Clin Chem 44(7):1535–1539

    PubMed  CAS  Google Scholar 

  18. Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24(18):2932–2947

    Article  PubMed  CAS  Google Scholar 

  19. Bjarnadottir M, Grubb A, Olafsson I (1995) Promoter-mediated, dexamethasone-induced increase in cystatin C production by HeLa cells. Scand J Clin Lab Invest 55(7):617–623

    Article  PubMed  CAS  Google Scholar 

  20. Takahashi T, Nakamura Y, Tsuya A, Murakami H, Endo M, Yamamoto N (2011) Pharmacokinetics of aprepitant and dexamethasone after administration of chemotherapeutic agents and effects of plasma substance P concentration on chemotherapy-induced nausea and vomiting in Japanese cancer patients. Cancer Chemother Pharmacol 68(3):653–659

    Article  PubMed  CAS  Google Scholar 

  21. Nakade S, Ohno T, Kitagawa J, Hashimoto Y, Katayama M, Awata H, Kodama Y, Miyata Y (2008) Population pharmacokinetics of aprepitant and dexamethasone in the prevention of chemotherapy-induced nausea and vomiting. Cancer Chemother Pharmacol 63(1):75–83

    Article  PubMed  CAS  Google Scholar 

  22. Fehrenbacher N, Bastholm L, Kirkegaard-Sorensen T, Rafn B, Bottzauw T, Nielsen C, Weber E, Shirasawa S, Kallunki T, Jaattela M (2008) Sensitization to the lysosomal cell death pathway by oncogene-induced down-regulation of lysosome-associated membrane proteins 1 and 2. Cancer Res 68(16):6623–6633

    Article  PubMed  CAS  Google Scholar 

  23. Seo HR, Bae S, Lee YS (2009) Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer 124(8):1794–1801

    Article  PubMed  CAS  Google Scholar 

  24. Bijnsdorp IV, Peters GJ, Temmink OH, Fukushima M, Kruyt FA (2010) Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int J Cancer 126(10):2457–2468

    PubMed  CAS  Google Scholar 

  25. Miki I, Tamura T, Nakamura T, Makimoto H, Hamana N, Uchiyama H, Shirasaka D, Morita Y, Yamada H, Aoyama N, Sakaeda T, Okumura K, Kasuga M (2005) Circadian variability of pharmacokinetics of 5-fluorouracil and CLOCK T3111C genetic polymorphism in patients with esophageal carcinoma. Ther Drug Monit 27(3):369–374

    Article  PubMed  CAS  Google Scholar 

  26. Martino S, Tiribuzi R, Ciraci E, Makrypidi G, D’Angelo F, di Girolamo I, Gritti A, de Angelis GM, Papaccio G, Sampaolesi M, Berardi AC, Datti A, Orlacchio A (2011) Coordinated involvement of cathepsins S, D and cystatin C in the commitment of hematopoietic stem cells to dendritic cells. Int J Biochem Cell Biol 43(5):775–783

    Article  PubMed  CAS  Google Scholar 

  27. Grzonka Z, Jankowska E, Kasprzykowski F, Kasprzykowska R, Lankiewicz L, Wiczk W, Wieczerzak E, Ciarkowski J, Drabik P, Janowski R, Kozak M, Jaskolski M, Grubb A (2001) Structural studies of cysteine proteases and their inhibitors. Acta Biochim Pol 48(1):1–20

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a Grant-in-Aid for Young Scientists from Japan Society for the Promotion of Science.

Conflict of interest

None of the authors has any former or present conflict of interest related to this study.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Manabu Kume, Takeshi Hirano & Midori Hirai

  2. Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan

    Hiroyuki Yasui & Yutaka Yoshikawa

  3. Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji, 670-8524, Japan

    Masanori Horinouchi & Tsutomu Nakamura

  4. Department of Clinical Laboratory, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Kanae Higashiguchi & Yoko Kobayashi

  5. Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Daisuke Kuroda

Authors
  1. Manabu Kume
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroyuki Yasui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yutaka Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masanori Horinouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kanae Higashiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoko Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daisuke Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takeshi Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Midori Hirai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tsutomu Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tsutomu Nakamura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kume, M., Yasui, H., Yoshikawa, Y. et al. Transient elevation of serum cystatin C concentrations during perioperative cisplatin-based chemotherapy in esophageal cancer patients. Cancer Chemother Pharmacol 69, 1537–1544 (2012). https://doi.org/10.1007/s00280-012-1860-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-012-1860-8

Keywords

Search

Navigation