Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 77, Issue 2, pp 333–338 | Cite as

A pharmacokinetic analysis of cisplatin and 5-fluorouracil in a patient with esophageal cancer on peritoneal dialysis

  • Jennifer R. EadsEmail author
  • Jan H. Beumer
  • Lavinia Negrea
  • Julianne L. Holleran
  • Sandra Strychor
  • Neal J. Meropol
Original Article

Abstract

Background

Very little is known about the pharmacokinetics of chemotherapeutic agents in patients also being treated with continuous ambulatory peritoneal dialysis. We sought to evaluate the pharmacokinetics of cisplatin and 5-fluorouracil in plasma and peritoneal dialysate in a patient being treated for esophageal adenocarcinoma.

Methods

A single patient with esophageal adenocarcinoma and on peritoneal dialysis for end-stage renal disease was treated with cisplatin 25 mg/m2 on day 1 of weeks 1 and 5 and continuous infusional 5-fluorouracil 1000 mg/m2/day on days 1–4 of weeks 1 and 5 along with daily radiation therapy. Intense plasma and dialysate sampling was performed during the week 5 administration, followed by quantitation of platinum by atomic absorption spectrophotometry and 5-fluorouracil by LC–MS/MS.

Results

Following systemic administration, clearance of ultrafilterable (active) platinum over the first 6 h was 20.8 L/h, which is lower than previously reported clearance levels of ultrafilterable platinum. Total platinum AUC was 131 μg h/mL, also higher than an AUC previously reported for total platinum in patients with normal renal function. Platinum-related material was detected in the peritoneal cavity, but this is likely inactive. 5-Fluorouracil penetrated the intraperitoneal cavity, but the contribution of peritoneal dialysis to drug clearance was negligible at 0.072 %.

Conclusions

Administration of intravenous cisplatin and 5-fluorouracil chemotherapy to a patient treated with continuous ambulatory peritoneal dialysis is feasible, but clearance in dialysate is nominal, thus suggesting that dose reduction is indicated for cisplatin. Systemic drug administration results in limited intraperitoneal penetration of 5-fluorouracil and inactive platinum species.

Keywords

Cisplatin 5-Fluorouracil Pharmacokinetics Peritoneal dialysis 

Notes

Acknowledgments

This project was supported by the Case Comprehensive Cancer Center (P30CA043703), Case Western Reserve University Clinical and Translational Science Collaborative (UL1TR000439) and the University of Pittsburgh Cancer Institute Cancer Pharmacokinetics and Pharmacodynamics Facility (P30CA047904). Dr. Eads is a recipient of a K12 Paul Calabresi Scholar Award (2K12CA076917-17).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Venook AP, Egorin MJ, Rosner GL, Hollis D, Mani S, Hawkins M, Byrd J, Hohl R, Budman D, Meropol NJ, Ratain MJ (2000) Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or renal dysfunction: cancer and Leukemia Group B 9565. J Clin Oncol 18:2780–2787PubMedGoogle Scholar
  2. 2.
    Venook AP, Enders Klein C, Fleming G, Hollis D, Leichman CG, Hohl R, Byrd J, Budman D, Villalona M, Marshall J, Rosner GL, Ramirez J, Kastrissios H, Ratain MJ (2003) A phase I and pharmacokinetic study of irinotecan in patients with hepatic or renal dysfunction or with prior pelvic radiation: CALGB 9863. Ann Oncol 14:1783–1790CrossRefPubMedGoogle Scholar
  3. 3.
    Okuyama M, Motoyama S, Maruyama K, Ohta H, Tsuchiya N, Oyake J, Ogawa J (2005) Chemotherapy for an esophageal cancer patient undergoing continuous ambulatory peritoneal dialysis for chronic renal failure and measurement of plasma concentration of the drug. Gan To Kagaku Ryoho 32:1029–1032PubMedGoogle Scholar
  4. 4.
    Sebestyen J, Garg U, Lewing KB, Warady BA, Abdel-Rahman S, Blowey DL (2010) Cisplatin pharmacokinetics in a child receiving peritoneal dialysis. Pediatr Nephrol 25:1185–1189CrossRefPubMedGoogle Scholar
  5. 5.
    Tomita M, Kurata H, Aoki Y, Tanaka K, Kazama JJ (2001) Pharmacokinetics of paclitaxel and cisplatin in a hemodialysis patient with recurrent ovarian cancer. Anticancer Drugs 12:485–487CrossRefPubMedGoogle Scholar
  6. 6.
    Zahra MA, Taylor A, Mould G, Coles C, Crawford R, Tan LT (2008) Concurrent weekly cisplatin chemotherapy and radiotherapy in a haemodialysis patient with locally advanced cervical cancer. Clin Oncol (R Coll Radiol) 20:6–11CrossRefGoogle Scholar
  7. 7.
    Arai Y, Oyama T, Hotta K, Tomori A, Miyata Y (2008) Successful treatment with 5-fluorouracil and cis-dichlorodiammineplatinum combined with 60 Gy of radiation in a case of advanced esophageal cancer complicated with chronic renal failure treated with hemodialysis. Nihon Shokakibyo Gakkai Zasshi 105:1482–1488PubMedGoogle Scholar
  8. 8.
    Cho H, Imada T, Masudo K, Doi C, Inaba M, Tokunaga M, Takanashi Y (2000) Combined 5-FU and CDDP in a gastric cancer patient undergoing hemodialysis—pharmacokinetics of 5-FU and CDDP. Gan To Kagaku Ryoho 27:2135–2138PubMedGoogle Scholar
  9. 9.
    Watanabe R, Takiguchi Y, Moriya T, Oda S, Kurosu K, Tanabe N, Tatsumi K, Nagao K, Kuriyama T (2003) Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer. Br J Cancer 88:25–30PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL (1999) Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA 281:1623–1627CrossRefPubMedGoogle Scholar
  11. 11.
    National Comprehensive Cancer Network (NCCN) Clinical practice guidelines in oncology, esophageal and esophagogastric junction cancers version 3. 2015. http://www.nccn.org. Accessed 21 Sept 2015
  12. 12.
    Kosovec JE, Egorin MJ, Gjurich S, Beumer JH (2008) Quantitation of 5-fluorouracil (5-FU) in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 22:224–230CrossRefPubMedGoogle Scholar
  13. 13.
    Colville H, Dzadony R, Kemp R, Stewart S, Zeh HJ 3rd, Bartlett DL, Holleran J, Schombert K, Kosovec JE, Egorin MJ, Beumer JH (2010) In vitro circuit stability of 5-fluorouracil and oxaliplatin in support of hyperthermic isolated hepatic perfusion. J Extra Corpor Technol 42:75–79PubMedCentralPubMedGoogle Scholar
  14. 14.
    Urien S, Lokiec F (2004) Population pharmacokinetics of total and unbound plasma cisplatin in adult patients. Br J Clin Pharmacol 57:756–763PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335:1950–1955CrossRefPubMedGoogle Scholar
  16. 16.
    Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J (2001) Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 19:1001–1007PubMedGoogle Scholar
  17. 17.
    Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LF, Walker JL, Burger RA (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354:34–43CrossRefPubMedGoogle Scholar
  18. 18.
    Cristea M, Han E, Salmon L, Morgan RJ (2010) Practical considerations in ovarian cancer chemotherapy. Ther Adv Med Oncol 2:175–187PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Ikeda K, Terashima M, Kawamura H, Takiyama I, Koeda K, Takagane A, Sato N, Ishida K, Iwaya T, Maesawa C, Yoshinari H, Saito K (1998) Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a comparative study of three different schedules of cisplatin administration. Jpn J Clin Oncol 28:168–175CrossRefPubMedGoogle Scholar
  20. 20.
    Gusella M, Rebeschini M, Cartei G, Ferrazzi E, Ferrari M, Padrini R (2005) Effect of hemodialysis on the metabolic clearance of 5-fluorouracil in a patient with end-stage renal failure. Ther Drug Monit 27:816–818CrossRefPubMedGoogle Scholar
  21. 21.
    Grem JL (2000) 5-fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs 18:299–313CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Jennifer R. Eads
    • 1
    Email author
  • Jan H. Beumer
    • 2
    • 3
  • Lavinia Negrea
    • 4
  • Julianne L. Holleran
    • 2
  • Sandra Strychor
    • 2
  • Neal J. Meropol
    • 1
  1. 1.University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandUSA
  2. 2.Cancer Therapeutics ProgramUniversity of Pittsburgh Cancer InstitutePittsburghUSA
  3. 3.Department of Pharmaceutical SciencesUniversity of Pittsburgh School of PharmacyPittsburghUSA
  4. 4.Division of Nephrology and Hypertension, University Hospitals Case Medical CenterCase Western Reserve UniversityClevelandUSA

Personalised recommendations